MX2008014771A - Piperidine derivatives as human papilloma virus inhibitors. - Google Patents

Abstract

HPV inhibitors with formula (I) where G1 represents a hydrocarbonated bond or chain possibly substituted by one or two alkyl groups, G2 represents a group (see formula Ia+Ib) or R represents a hydrogen, an alkyl, halogenoalkyl, or a prodrug radical such as carbamate, acetyl or dialkylaminomethyl, G represents a bond or a hydrocarbonated chain possibly substituted by one or two alkyls, W represents an oxygen or sulphur, R1 and R2 each represent a group chosen from among hydrogen, halogen, hydroxyl, thio, alkoxy, halogenoalkoxy, alkylthio, halogenoalkylthio, amino, monoalkylamino, dialkylamino, cycloalkyl, alkyl or halogenoalkyl, R3 represents an acid or a prodrug radical of the acid function or a bioisostere of the acid function, A represents an aryl, cycloalkyl, cycloalkenyl or a heterocycle, each possibly substituted, and B represents an aryl or a heterocycle with 6 chains, each possibly substituted, and pharmaceutically acceptable salts.

Description

DERIVATIVES OF PIPERIDINE AS INHIBITORS OF THE HUMAN PAPILLOMA VIRUS The present invention relates to novel antiviral compounds directed against the papilloma virus, with pharmaceutical compositions containing the same, with its method of preparation and synthesis intermediates, as well as with its use to treat or prevent an infection with the papilloma virus. . Papilloma viruses are viruses without cover, the genome of which is formed by double-stranded DNA of approximately 8 kb. They are widely dispersed in nature and cause epithelial lesions in humans, as well as in many animals, including rabbits, horses, dogs and bovine species. More than one hundred human papilloma viruses (HPV) have been described. They are classified depending on their site of infection. Approximately 30 HVP have been isolated from the anogenital mucosa (cervix of the uterus, vagina, vulva, penis, anus, rectum). The other HPVs are associated with skin lesions. HPVs with cutaneous tropism include, a, HPV1, HPV2, HPV3, HPV4, HPV5, HPV7, HPV8, HPV9, HPV10, HPV12, HPV14, HPV17, HPV19, HPV20, HPV21, HPV22, HPV23, HPV24, HPV25, HPV26 , HPV27, HPV28, HPV29, HPV38, HPV41, HPV47, HPV49. They are associated with lesions such as warts (common wart, plantar wart, verruca mirmecia, superficial wart, flat wart, ...), and diseases such as verrucous epidermodysplasia.

HPV of the mucogenital type are involved in laryngeal and anogenital diseases including certain cancers. They are often classified as high risk HPV and low risk HPV, with reference to the type of injuries with which they are associated. Low-risk HPVs include, .a., HPV6, HPV11, HPV13, HPV32, HPV34, HPV40, HPV42, HPV43, HPV44, HPV53, HPV54, HPV55, HPV57, HPV58, HPV74, HPV91. Low-risk HPVs are associated with benign lesions such as condylomata (genital warts, such as condylomata acuminata and flat condylomata), laryngeal papillomas, conjunctival or buccal papillomas, or other epithelial lesions such as low-grade intraepithelial neoplasms or recurrent respiratory papillomatosis. and more rarely, with bowenoid papulosis or high-grade intraepithelial neoplasms with carcinomas. High-risk HPVs include, La., HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV59, HPV61, HPV62, HPV66, HPV67, HPV68, HPV72. They are involved in low-grade intraepithelial lesions that can develop into higher-grade lesions to cancers, in particular, cancer of the uterine cervix and other anogenital cancers. Genital HPV infections are the most common sexually transmitted infections in the world, including in developed countries, with more than 20 million people infected in the United States. The prevalence of HPV infections varies from 3-42% depending on the countries and affects 10-20% of the sexually active population in industrialized countries. In part of this population the infection persists, and can lead to cancers in the case of high-risk HPV. The prevalence of genital warts (condylomas) is estimated to be 1-2% in the sexually active population of industrialized countries, that is, approximately 3,500,000 new cases each year in these countries and 28,000,000 worldwide. Genital warts can be found on parts of the body that include the anus, vulva, vagina, cervix of the uterus or penis or peripheral bodies to them. The treatments of genital warts are based on several strategies, physical destruction (cryotherapy, CO2 laser, electrosurgery, surgical excision), application of cytotoxic agents (TCA, podophyllin, podofilox), until the application of immunomodulatory agents (interferon, imiquimod). However, none of these methods completely eliminates all viral particles, and significant proportions of recurrence are observed, accompanied by severe side effects with the present therapeutic strategies. This reinforces the need for new strategies to control or eliminate infections with papilloma viruses. Unlike what exists in the treatment of other viral diseases, such as those caused by HIV, herpes viruses or influenza viruses, to date, there is no antiviral treatment that specifically selects the viral pathogens that they are the papilloma viruses. Papilloma viruses infect epithelia with multiple strata and their viral cycle is closely related to the organogenesis of these organs and to the differentiation of keratinocytes. After infection, the viral genome is present and is replicated in a small number in the basal cells of the epithelium. As the cells gradually differentiate, the expression of the viral genes and the number of copies of the viral genome increases until the expression of the viral capsid genes and the formation of infectious virions in all the differentiated keratinocytes. The genome of HPV potentially encodes approximately ten proteins. The proteins expressed initially, E1 and E2, are involved in the replication of the viral genome and the regulation of the expression of viral genes. The other initial proteins of these viruses (E4, E5, E6, E7) have functions in relation to the proliferation of cells or roles that have not yet been fully explained. The existence of the E3 and E8 proteins is still uncertain. The subsequent proteins L1 and L2 are those that form the viral capsid. The only 2 viral proteins required and sufficient to replicate HPV are E1 and E2. They are able to form an E1 / E2 complex and to bind to the origin of replication (Oh) of HPV, a sequence contained in the viral genome and carrying nearby sites recognized by E1 and by E2. E2 is capable of binding E2 sites with very high affinity, whereas E1, alone, does not have a very high affinity for E1 sites. The interaction between E1 and E2 increases the binding of E1 in Oh by cooperative binding to DNA. Once it binds to DNA, E1 no longer interacts with E2, but instead forms a hexamer. The activities of the helicase and the ATPase of E1 allow the unfolding of the viral DNA that is then replicated by the cellular replication mechanism. The inventors have sought to develop small molecules that inhibit the replication of HPV, preferably with a low risk, significantly interfering with the formation of the complex between the E1 and E2 proteins. A solution was found by elaborating new derivatives. The object of the present invention are these novel derivatives, their synthesis, as well as their use in pharmaceutical compositions capable of being used in the prevention and treatment of pathologies related to the inhibition of HPV replication, such as for example, HPV1, HPV2 , HPV3, HPV4, HPV5, HPV7, HPV9, HPV9, HPV12, HPV12, HPV14, HPV15, HPV17, HPV19, HPV20, HPV21, HPV22, HPV23, HPV25, HPV25, HPV27, HPV28, HPV29, HPV38, HPV41, HPV47 , HPV4, HPV1, HPV1, HPV13, HPV32, HPV34, HPV40, HPV42, HPV43, HPV44, HPV53, HPV54, HPV55, HPV57, HPV58, HPV74, HPV16, HPV18, HPV18, HPV33, HPV33, HPV39, HPV39, HPV45, HPV51, HPV52, HPV56, HPV59, HPV61, HPV61, HPV66, HPV67, HPV68, HPV72, preferably, low risk HPVs such as HPV6, HPV11, HPV13, HPV32, HPV34, HPV40, HPV42, HPV43, HPV44, HPV53, HPV54, HPV55, HPV57, HPV58, HPV74, HPV91. The novel derivatives, objects of the present invention, are active against the papilloma virus. These are also capable of inhibiting the interaction of E1 / E2. Within the scope of the present invention, the following definitions are provided: "Alkyl" or "Alk" means a saturated, monovalent or divalent, linear or branched hydrocarbon chain, comprising from 1-6 carbon atoms, such as the methyl, ethyl, propyl, isopropyl, tert-butyl, methylene, ethylene, propylene group ... "Acyl" means a -COR group, wherein R is an alkyl group as defined above or a phenyl group , for example, an acetyl group, ethylcarbonyl, benzoyl ... "Acylamino" means a group -NHC (O) R, wherein R is an alkyl group as defined at the beginning. Acylaminoalkyl "means a group -AlkNHC (O) R, wherein Alk and R are alkyl groups as defined above" "Alkoxy" means an -Oalk group, wherein Alk is an alkyl group as defined above. , for example, methoxy, ethoxy, n-propyloxy, tert-butyloxy ...

"Aryl" means a monocyclic or bicyclic aromatic system comprising from 4-10 carbon atoms, it being understood that in the case of a bicyclic system, one of the rings has an aromatic character and the other ring is aromatic or unsaturated. Aryl comprises, for example, phenyl, naphthyl, indenyl, benzocyclobutenyl, ... "heterocycle" means a monocyclic or bicyclic saturated, unsaturated or aromatic, fused, spirited or bridged 3-12 membered monocyclic or bicyclic system, comprising 1-4 heteroatoms, either identical or different, selected from oxygen, sulfur and nitrogen, and possibly containing 1 or 2 oxo or thioxo groups, it being understood that in the case of a bicyclic system, one of the rings may have an aromatic character and the other ring It is aromatic or unsaturated. Heterocycle comprises, for example, the piperidyl, piperazyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridyl, pyrimidyl, pyrazinyl, pyrazinyl, benzofuryl, benzothienyl, indolyl, quinolyl, isoquinolyl, benzodioxolyl, benzodioxinyl, benzo [1, 2, 5] thiadiazolyl, benzo [1, 2,5] oxadiazolyl, [1, 2,3] triazolyl, [1, 2,4] triazolyl, ... "Alkylthio" means a group -Salk, where Alk is a group alkyl as defined at the beginning. Alkylthio comprises, for example, methylthio, ethylthio, isopropylthio, heptylthio, ... "Arylalkyl" means a group -Alk-Ar, wherein Alk represents an alkyl group as defined at the beginning, and Ar represents an aryl group as defined at first.

"Halogen atom" means a fluorine, bromine, chlorine or iodine atom. "Cycloalkyl" means a monocyclic or bicyclic saturated, fused or bridged system comprising 3-12 carbon atoms, such as the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, decalinyl, norbornyl, ... " "Cycloalkenyl" means an unsaturated monocyclic or bicyclic, fused or bridged system, comprising 3-12 carbon atoms, such as the cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, ... "Monoalkylamino" means a -NHAIk group, wherein Alk is an alkyl group as defined at the beginning. "Dialkylamino" means a group -NAIkAlk ', wherein Alk and Alk', each represents, independently of one another, an alkyl group as defined at the beginning. "Monoalkylamide" means a group -C (0) NHAIk, wherein Alk is an alkyl group as defined at the beginning. "Dialkylamide" means a group -C (O) NAIkAlk ', wherein Alk and Alk' each independently represents one alkyl group as defined above. "N-cycloalkyl" means a cycloalkyl radical as defined above, comprising a nitrogen atom, attached to the rest of the molecule through this atom. N-cycloalkyl, for example, comprises the piperid-1-yl or pyrrolid-1-yl group. "N-cycloalkenyl" means a cycloalkenyl radical as defined above, comprising a nitrogen atom, attached to the rest of the molecule through this atom. N-cycloalkenyl, for example, comprises the tetrahydropyridin-1-yl group. "Haloalkyl" means a saturated, linear or branched hydrocarbon chain, comprising 1-6 carbon atoms and substituted with 1-6 halogen atoms such as the trifluoromethyl group, 2,2,2-trifluoroethyl, ... "Haloalkoxy "means a saturated, branched or linear hydrocarbon chain, comprising 1-6 carbon atoms and substituted with 1-6 halogen atoms, the chain is linked to the compound through an oxygen atom, such as the trifluoromethoxy group, 2,2,2-trifluoroethoxy, ... "Haloalkylthio" means a saturated, linear or branched hydrocarbon chain, comprising 1-6 carbon atoms and substituted with 1-6 halogen atoms, the chain being attached through the sulfur atom, such as the trifluoromethylthio group, ... "Protective group" or "protecting group" means the group that selectively blocks the reactive site in a multifunctional compound, so that a chemical reaction can be carried out in a select manner Iiva in another unprotected reactive site, in the sense conventionally associated with the latest in chemical synthesis.

"Isomerism" means compounds that have identical molecular formulas but that differ in nature or in the sequence of union of their atoms or in the arrangement of their atoms in space. The isomers that differ in the arrangement of their atoms in space are designated as "stereoisomers". Stereoisomers that are not mirror images of one another are designated as "diastereomers", and stereoisomers that are non-superimposed images in a mirror are designated as "enantiomers" or optical isomers. "Stereoisomers" refers to racemates, enantiomers and diastereoisomers. "Pharmaceutically acceptable" means that it is generally safe, non-toxic, and that it is not biologically undesirable, both for veterinary use and for human pharmaceutical use. "Pharmaceutically acceptable salts" of a compound means salts that are pharmaceutically acceptable as defined herein and that have the desired pharmacological activity of the parent compound. It should be understood that all references to the pharmaceutically acceptable salts comprise the solvent addition forms (solvates) or the crystalline forms (polymorphic forms) as defined herein, of the same acid addition salts or bases. A review of pharmaceutically acceptable salts is described remarkably in J. Pharm. Sci., 1977, 66, 1 -19. "Pharmaceutically acceptable acids" means the non-toxic acid salts derived from organic or mineral acids. Among the pharmaceutically acceptable acids, non-limiting mention may be made of hydrochloric, hydrobromic, sulfuric, phosphonic, nitric, acetic, trifluoroacetic, lactic, pyruvic, malonic, succinic, glutaric, fumaric, tartaric, maleic, citric, ascorbic acids , oxalic, methanesulfonic, camphoric, benzoic, toluenesulfonic, ... "Pharmaceutically acceptable bases" means non-toxic basic salts derived from organic or mineral bases, formed when an acidic proton present in the main compound is replaced by a metal ion or is coordinated to an organic base. Among the pharmaceutically acceptable bases, mention may be made non-limitingly to sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, triethylamine, terbutylamine, diethylaminoethanol, ethanolamine, ethylenediamine, dibenzylethylenediamine, piperidine, pyrrolidine, morpholine, piperazine, benzylamine, arginine, lysine, histidine, glucosamine, quaternary ammonium hydroxides, ... "Prodrug" means a chemical derivative of the compound object of the present invention, which generates the compound in vivo by means of a spontaneous chemical reaction with the physiological medium, notably by an enzymatic reaction, a photolysis and / or a metabolic reaction. By "radical of the prodrug of the acid function" is meant a labile functional group that will generate an acid function in vivo after separating from the compound object of the present invention, by means of a spontaneous chemical reaction with the physiological medium, especially by means of an enzymatic reaction, photolysis and / or a metabolic reaction. The radicals of the prodrug with an acid function include, in particular, an ester, pivoyloxymethyl, acetoxymethyl, phthalidyl, indanyl, methoxymethyl or 5-R-2-oxo-1,3-dioxolen-4-ylmethyl group. Other examples are described in T. Higuchi and V. Stella, "Pro-drugs as Novel Delivery Systems", Vol. 14, A.C.S. Symposium Series, American Chemical Society (1975) and in "Bioreversible Carriers in Drug Design: Theory and Application", edited by E. B. Roche, Pergamon Press: New York, 14-21 (1987). In the present patent application, the chemical compounds are named according to the IUPAC nomenclature (The International Union of Pure and Applied Chemistry). The object of the present invention is a compound of formula (I): as well as its stereoisomers, wherein: d represents a saturated or branched saturated or linear saturated hydrocarbon chain or bond, comprising 1-4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, G2 represents a group R or W, wherein: R represents a hydrogen atom, an alkyl group, haloalkyl, or a prodrug radical, such as carbamate, acetyl, dialkylaminoethyl or -CH 2 -O-CO-Alk, • G represents a bond or a saturated or unsaturated hydrocarbon chain, linear or branched, comprising 1-4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, · W represents an oxygen atom, sulfur or NH, Ri and R2, whether identical or different, each represent a group selected from a hydrogen atom, a halogen atom, a hydroxyl group, thio, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, monoalkylamino, dialkylamino, cycloalkyl, alkyl or haloalkyl, R3 represents an acid group or a radical of the prodrug of the acid function such as an ester, or in addition a bioester of the acid function, such as a tetrazole, phosphonate, phosphonamide, sulfonate or sulfonamide, A represents an aryl group, cycloalkyl, cycloalkenyl or a heterocycle, each optionally substituted, and B represents an aryl group or a 6-membered heterocycle, each optionally substituted, as well as its pharmaceutically acceptable salts, A, as defined at the beginning, may be substituted with one or two groups, either identical or different, selected from: • a hydrogen atom, a halogen atom, • an alkoxy, alkylthio, haloalkoxy, haloalkylthio, hydroxyl, thio, cyano, amino, monoalkylamino or dialkylamino group, a group - SOnR ', -COR', -CO2R ', -OCOR', -CONR'R ", -NR'COR" or -NR'SO2R ", wherein R 'and R" each represents independently one of the other a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, • an alkyl or haloalkyl group, the alkyl group being optionally substituted with a cyano, amino, monoalkylamino, dialkylamino or acylamino group, • an aryl group, Arylalkyl, -X-aryl, -X-arylalkyl or -Alk-X-ari lo, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, each substituted on the aryl portion with one or two substituents, either identical or different, selected from: a hydrogen atom or a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano group, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide, ^ a group -SOn \ -COR ', -CO2R', -OCOR ', -CONR'R ", -NR'COR" or -NR 'SO2R', wherein R 'and R "each represents independently of one another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, • a heterocycle group, -Alk-heterocycle, -X-heterocycle, -X-Alk-heterocycle or -Alk-X-heterocycle, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, - SO-, -SO2-, -CO- or -CONH-, each optionally substituted on the heterocycle moiety with one or two substituents, either identical or different , selected from: a hydrogen atom or a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkyl or dialkylamino group, acid, ester, amide, mono or dialkylamide, or a group -SOnR "-COR", -CO2R ', -OCOR', -CONR'R ", -NR'COR" or -NR'SO2R ", wherein R 'and R" each represents independently of one another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, • a cycloalkyl group, -Alk-cycloalkyl, cycloalkenyl, -Alk-cycloalkenyl, -X-cycloalkyl, -X-Alk -cycloalkyl, -X-cycloalkenyl, -X-Alk-cycloalkenyl, -Alk-X-cycloalkyl, -Alk-X-cycloalkenyl, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -. -S-, -SO-, -S02-, -CO- or -CONH-, each optionally substituted in the cyclic portion with one or two substituents, either identical or different, selected from: a hydrogen atom or an atom of halogen, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide, or oxo or,? a group -SO "R \ -COR", -CO2R ', -OCOR', -CONR'R ", -NR'COR" or -NR'SO2R ", where R" and R "represents each independently one of the other a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, B as defined at the beginning may be an aryl or a 6-membered heterocycle, substituted in the ortho position with a group R 4 and optionally substituted with a group R5, wherein: • R4 represents: an alkyl group, -NHAIk, -NAIkAlk ', -NHcycloalkyl or -NAIkcycloalkyl, Alk and Alk' being identical or different, a cycloalkyl, cycloalkenyl, N-cycloalkyl or N-cycloalkenyl, each optionally substituted with one or two substituents, either identical or different, selected from a hydrogen atom, a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl group, cyano, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide, oxo or -X-aryl , and where X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, S02-, -CO- or -CONH-, or ^ a aryl group optionally substituted with one or two substituents, either identical or different, a hydrogen atom, a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide or -X-aryl, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, - SO-, -SO2-, -CO- or -CONH-, • R5 represents: a hydrogen atom or a halogen atom, a hydroxyl group, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, amino, monoalkylamino, dialkylamino, - NHacyl, cyano, acyl, acid, ester, amide, monoalkylamide or dialkylamide, an alkyl or haloalkyl group, the alkyl group may be substituted with a cyano, hydroxyl, alkoxy, acid or ester group, a group -SOnAlk, -SOnNH2, -SOnNHAIk or - SOnNAIkAlk ', where n have and the value of 1 or 2, and Alk and Alk 'are either identical or different, or a piperidine, oxopiperidine, morpholine group or in addition a piperazine group optionally substituted with an alkyl or acyl group, The preferred compounds are the compounds of formula (I), where: G- \ represents a bond or a saturated or unsaturated, straight or branched hydrocarbon chain, comprising 1-4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, G2 represents a group , wherein: R represents a hydrogen atom, an alkyl group, haloalkyl, or a prodrug radical, such as carbamate, acetyl, dialkylaminoethyl or -CH2-0-CO-Alk, • G represents a bond or a chain of hydrocarbon, comprising 1-4 carbon atoms, linear or branched, saturated or unsaturated, optionally substituted with one or two alkyl groups, preferably identical, and • W represents an oxygen, sulfur or NH, Ri and R2 atom whether identical or different, each represents a selected group of a hydrogen atom, a halogen atom, a hydroxyl group, thio, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, monoalkylamino, dialkylamino, cycloalkyl, alkyl or haloalkyl, R3 represents an acid group or a radical of the prodrug of the acid function such as an ester, or in addition a bioester of the acid function, such as a tetrazole, phosphonate, phosphonamide, sulfonate or sulfonamide, A represents an aryl group oh Eterocycle, each being optionally substituted with one or two groups, either identical or different, selected from: • a hydrogen atom, a halogen atom, • an alkoxy, alkylthio, haloalkoxy, haloalkylthio, hydroxyl, thio, cyano group, amino, monoalkylamino or dialkylamino, · a group -SOnR ', -COR', -C02R \ -OCOR ', -CONR'R ", -NR'COR "or -NR'SO2R", wherein R 'and R "each represents independently of one another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, • a alkyl or haloalkyl group, the alkyl group being optionally substituted with a cyano, amino, monoalkylamino, dialkylamino or acylamino group, • an aryl, arylalkyl, -X-aryl group, wherein X represents a group -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, each substituted on the aryl portion with one or two substituents, either identical or different, selected from: a hydrogen atom or a halogen atom, < / an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkylamino or dialkylamino group, acid, ester , amide, mono or dialkylamide, or "a group -SOnR ', -COR', -C02R ', -OCOR', -CONR'R", -NR'COR "or -NR'S02R", where R 'and R "represents each independently one of the or a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, • a heterocycle, -X-heterocycle, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, each optionally substituted on the heterocycle moiety with one or two substituents, either identical or different, selected from: a hydrogen atom or a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkyl or dialkylamino, acid, ester, amide, mono or dialkylamide, or a group -SOnR ', -COR', -CO2R ', -OCOR', -CONR'R ', -NR'COR' or -NR'SO2R ', where R' and R "each independently represents one of the another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, or · a cycloalkyl, cycloalkenyl, -X-cycloalkyl group, -X-cycloalkenyl, wherein X represents a group -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or - CONH-, each optionally substituted in the cyclic portion with one or two substituents either identical or different, selected from: a hydrogen atom or a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide, or oxo, or? a group -SOnR ', -COR', -CO2R ', -OCOR', -CONR'R ', -NR'COR' or -NR'SO2R ', wherein R' and R "each represents independently one on the other a hydrogen atom, an alkyl, haloalkyl, and n group has the value of 1 or 2, and B represents a phenyl or pyridine group: substituted in the ortho position with an N-cycloalkyl group such as piperidine or with a cyclohexyl, each optionally substituted with one or two substituents either identical or different, selected from a hydrogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, -X-aryl group, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, and / or optionally substituted with a halogen atom or with an alkyl or haloalkyl group. The compounds which are even more preferred are the compounds of formula (I), wherein: Gi represents a bond or a saturated or unsaturated, straight or branched hydrocarbon chain, comprising 1-4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, G2 represents a group , wherein: • R represents a hydrogen atom, an alkyl group, haloalkyl, or a prodrug radical, such as a carbamate, acetyl, dialkylaminoethyl or -CH2-O-CO-Alk, • G represents a bond or a chain saturated or unsaturated hydrocarbon, linear or branched, comprising 1 -4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, and · W represents an oxygen atom, sulfur or NH-, Ri and R2, whether identical or different, each represent a group selected from a hydrogen atom, a halogen atom, a hydroxyl group, thio, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, monoalkylamino, dialkylamino, cycloalkyl, alkyl or haloalkyl, R3 represents an acid group or a radical of the prodrug of the acid function such as an ester, or in addition a bioester of the acid function, such as a tetrazole, phosphonate, phosphonamide, sulfonate or sulfonamide, A represents an aryl group optionally substituted with one or both groups, either identical or different, selected from: • a hydrogen atom, a halogen atom, • an alkoxy, alkylthio, haloalkoxy, haloalkylthio, hydroxyl, thio, cyano, amino, monoalkylamino or dialkylamino group , a group -SOnR \ -COR ', -C02R \ -OCOR', -CONR'R ", -NR'COR" or -NR SO2R ", where R 'and R" represent each independently of each other a hydrogen atom, an alkyl, haloalkyl, and n group has the value of 1 or 2, "an alkyl or haloalkyl group, the alkyl group being optionally substituted with a cyano, amino, monoalkylamino, dialkylamino or acylamino group, • an aryl group , arylalkyl, -X-aryl, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, each substituted on the aryl moiety with one or two substituents, either identical or different, selected from: a hydrogen atom or a halogen atom, ^ an alkyl, haloalkyl, alkyl group oxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide, or a group -SOnR ', -COR', -C02R \ -OCOR ', -CONR'R ", -NR'COR" or -NR'SO2R ", wherein R 'and R" each represents independently of one another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, • a heterocycle, -X-heterocycle, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2 -, -CO- or -CONH-, each optionally substituted on the heterocycle moiety with one or two substituents, either identical or different, selected from: a hydrogen atom or a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide, or a group -SOnR \ -COR ', -CO2R', -OCOR ', - CONR'R ", -NR'COR" or -NR'SO2R ", where R 'and R" represent each one independently of one another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, or "a cycloalkyl or -X-cycloalkyl group, wherein X represents -O-, -NH -, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, each optionally substituted in the cyclic portion with one or two substituents, either identical or different, selected from a hydrogen atom, a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkylamino or dialkylamino group, acid, ester, amide, mono or dialkylamide or oxo, and B represents a phenyl or pyridine group: substituted in the ortho position with an N-cycloalkyl group such as piperidine with a cyclohexyl, each optionally substituted with one or two substituents, either identical or different , selected from a hydrogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, -X-aryl, in which e X represents a group -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, and / or optionally substituted with a halogen atom or with an alkyl or haloalkyl group. The most preferred compounds are the compounds of formula (I), wherein: G1 represents a bond or a saturated hydrocarbon chain 0 unsaturated, linear or branched comprising 1-4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, preferably a bond or a hydrocarbon chain comprising one or two carbon atoms, G2 represents a group. where n is an integer between 1 and 4, and m is an integer that has the value of 1 or 2, preferably n has the value of 1 or 2, R 1 represents an alkoxy group, such as methoxy, preferably in the ortho position relative to R 3, R 2 represents a hydrogen or halogen atom, such as chlorine or bromine, or an alkyl group, such as methyl, preferably at the meta position relative to R3, R3 represents an acid group or ester, A represents an aryl group such as phenyl, preferably substituted: in the meta position or for: • a halogen atom or an alkyl, haloalkyl, cyano, alkoxy, haloalkoxy, acylaminoalkyl or a -XR group, wherein X represents a group -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, and R represents an arylalkyl, cycloalkyl or aryl group, each optionally substituted with one or two substituents, either identical or different, such as a halogen atom, an alkoxy, alkyl, haloalkyl, cyano, acyl, amino, monoalkylamino or dialkylamino group, acid, ester, amide, mono or dialkylamide, or a group -SOnR \ -OCOR ', -NR'-COR "or -R'SO2R", wherein R' and R "represent each independently of each other an hydrogen, an alkyl, haloalkyl group, and n has the value of 1 or 2, or • a cycloalkyl, aryl, arylalkyl or heterocycle group, preferably N-cycloalkyl, each optionally substituted with one or two substituents, either identical or different, such as a halogen atom, an alkoxy, alkyl, haloalkyl, cyano, acyl, amino, monoalkylamino or dialkylamino group, acid, ester, amide, mono or dialkylamide, or a group -SOnR \ -OCOR ', -NR' COR "or -NR'S02R" ', wherein R' and R "each independently represents one hydrogen atom, an alkyl, haloalkyl group and n has the value of 1 or 2, and / or ortho or meta position with an alkyl group, and B represents an aryl group, preferably a phenyl, substituted in the ortho position with a heterocycle group, preferably an N-cycloalkyl, such as a piperidine group, and / or • substituted in the ortho position with an alkyl group, such as a methyl. The most preferred compounds are the compounds of formula (I), wherein: Gi represents a bond or a saturated or unsaturated, straight or branched hydrocarbon chain, comprising 1-4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, in a manner preferred a bond or a hydrocarbon chain comprising 1 or 2 carbon atoms, G2 represents a group H wherein n is an integer between 1 and 4, and m is an integer having the value of 1 or 2, preferably n has the value of 1 or Ri represents an alkoxy group, such as methoxy, preferably in the ortho position relative to R3, R2 represents a hydrogen or halogen atom, such as chlorine or bromine, or an alkyl group, such as methyl, preferably in the meta position in relation to R3, R3 represents an acid or ester group, A represents an aryl group such as phenyl, preferably substituted: in the meta or para position with: • a halogen atom or a cyano, alkoxy, haloalkoxy, acylaminoalkyl or -XR group, wherein X represents -O-, -S-, -SO-, -SO2- or -CO- and R represents an arylalkyl, cycloalkyl or aryl group, each optionally substituted with one or two substituents, either identical or different, such as a halogen atom, an alkoxy or acyl group, or • a cycloalkyl, aryl or aryl group alkyl, each optionally substituted with one or two substituents, either identical or different, such as an acyl or alkoxy group, and and / or in the ortho or meta position with an alkyl group, and B represents an aryl group, preferably a phenyl substituted in the ortho position with a heterocycle group, preferably an N-cycloalkyl, such as a piperidine group, and / or substituted in the ortho position with an alkyl group, such as methyl.

The most preferred compounds are the compounds of formula (I), wherein: d represents a bond or a saturated or unsaturated, straight or branched hydrocarbon chain, comprising 1-4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, in a manner preferred a bond or a hydrocarbon chain comprising 1 or 2 carbon atoms, G2 represents a group H wherein n is an integer between 1 and 4, preferably n has the value of 1, Ri represents an alkoxy group, such as methoxy, preferably in the ortho position relative to R3, R2 represents a hydrogen or halogen atom, such as chlorine or bromine, or an alkyl group, such as methyl, preferably at the meta position relative to R3, R3 represents an acid group or ester, A represents an aryl group, as a phenyl, preferably substituted at the meta or para position with: • a halogen atom or an alkoxy, haloalkoxy or -XR group, wherein X represents -O- and R represents an arylalkyl, cycloalkyl or aryl group, each one optionally substituted with one or two substituents, either identical or different, such as a halogen atom, an alkoxy group or acyl, or • a cycloalkyl, aryl or arylalkyl group, each substituted optionally with one or two substituents, either identical or different, such as an acyl group, and B represents an aryl group, preferably a phenyl, • substituted in the ortho position with a heterocycle group, preferably a N-cycloalkyl, such as a piperidine group, and / or • substituted in the ortho position with an alkyl group, such as a methyl.

The even more preferred compounds are grouped in Table I: TABLE I 1 5-Bromo-2-methoxy-4- [N- (4-methoxy-phenyl) -N- (2- (piperidin-1-yl-phenyl) -hydrazinocarbonyl-methyl] -benzoic acid hydrochloride 2 Acid chlorohydrate 5-Bromo-2-methoxy-4- [N- (2-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxy-phenyl) -hydrazinocarbonyl-methyl] -benzoic acid 3-Bromo-2-hydrochloride -methoxy-4- [N- (3-methoxy-benzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -benzoic acid 4- [N- (4-benzyloxy-phenyl)] -hydrochloride -N- (2-piperidin-1-yl-phenyl) hydrazinocarbonylmethyl] -5-bromo-2-methoxy-benzoic acid 5-Bromo-4-. {N- [4- (4-fluoro-phenoxy) hydrochloride ) -phenyl] -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl} -2-methoxy-benzoic acid 6-bromo-2-methoxy-4- {N- [2- Hydrochloride (4-methoxy-phenyl) -ethyl] -N-2-piperidin-1-yl-phenyl) -hydrazino-carbonylmethyl} -benzoic acid 7-bromo-2-methoxy-4- [N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine-carbonylmethyl] -hydrochloride benzoic acid 5-Bromo-2-methoxy-4- [N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-phenyl) -hydrazine-carbonylmethyl] -benzoate of methyl 5-bromo-2-methoxy-4- [N- (4-methoxy-benzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -benzoic acid hydrochloride 5-bromohydrochloride -4- [N- (4-cyclohexyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -2-methoxy-benzoic acid hydrochloride 5-bromo-2-methoxy-4- [ N- (2-methyl-6-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxy-phenyl) -hydrazino-carbonylmethyl] -benzoic acid Hydrochloride of 5-bromo-2-methoxy-4- [ N- (4'-methoxy-biphenyl-4-yl) - N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonyl-methyl] -benzoic acid Hydrochloride of 5-bromo-4- [N- (4- cyclohexyloxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -2-methoxy-benzoic acid 5-Bromo-2-methoxy-4- [N- (4-phenoxy-phenyl) hydrochloride] -N- (2- pip eridin-1-yl-phenyl) -hydrazinocarbonylmethyl] -benzoic acid 5-bromo-4- hydrochloride. { N- [4- (4-chloro-phenoxy) -phenyl] -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl} -2-methoxy-benzoic acid 4- Hydrochloride. { N- [4- (4-Fluoro-phenoxy) -phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl} -2-methoxy-benzoic acid 5-bromo-4- hydrochloride. { N- [4- (4-Fluoro-phenoxy) -phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazino-carbonyl-methyl} -2-methoxy-benzoic to 5-Bromo-4-. { N- [4- (4-Fluoro-phenoxy) -phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazino-carbonyl-methyl} Methyl -2-methoxybenzoate 4- [N- (4-benzyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-bromo-2-methoxy-benzoic acid hydrochloride hydrochloride 4- [N- (4-bromophenyl) -N- (2-piperidin-1-yl-phenyl) - hidracinocarbonilmetil] -5-chloro-2-methoxy-benzoic acid hydrochloride 4- [N- (3'-acetyl-biphenyl-4-yl) -N- (2-piperidin-1-yl- phenyl) -hidracinocarbonilmetil] -5-chloro-2-methoxy-benzoic acid hydrochloride 4- [N- (4 ' -acetyl-biphenyl-4-yl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-chloro-2-mexoti-benzoic acid 5-bromo-2-methoxy-4- [-] hydrochloride N- (3-phenoxy) -phenyl] -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -benzoic acid 5-Bromo-2-methoxy-4- [N- (4-phenylsulfanyl) hydrochloride) -phenyl] - N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -benzoic acid 4- [N- (4-benzenesulfonyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrochloride] ) -hydrazinocarbonylmethyl] -5-bromo-2-methoxy-benzoic acid 4- [N- (4-benzenesulfinyl-phenyl) -N- (2-piperidin-1-hydrochloride il-phenyl) -hydrazinocarbonylmethyl] -5-bromo-2-methoxy-benzoic acid 2-methoxy-4- hydrochloride. { (E) -2- [N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonyl] -vinyl} -benzoic acid 5-bromo-2-methoxy-4- hydrochloride. { (E) -2- [N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine-carbonyl] -vinyl} -benzoic acid 4- [N- (4-benzyl-phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-bromo-2-methoxy-benzoic acid hydrochloride acid hydrochloride 5-bromo-2-methoxy-4- [N- (4'-methoxy-biphenyl-4-yl) - N- (2-methyl-6-piperidin-1-yl-phenyl) -hidracino-carbonyl -methyl] -benzoic acid 30 4- [N- (Acetylamino-methyl) -phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-bromo-2-methoxy-benzoic acid hydrochloride 31 Hydrochloride of 5-bromo-4- [N- (4-cyano-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -2-methoxy-benzoic acid 32 4- [N- (4'-Acetyl-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-bromo-2-methoxy acid hydrochloride - benzoic 33 5-bromo-2-methoxy-4- [N- (4'-methoxy-2-methyl-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl) hydrochloride phenyl) -hydrazinocarbonylmethyl] -benzoic acid The object of the present invention are also the pharmaceutical compositions comprising at least one compound of Formula (I), associated with a pharmaceutically acceptable excipient.

The pharmaceutical compositions according to the invention, they can be compositions that can be administered in the body via any route of administration. In a non-exhaustive way, the route of administration of the pharmaceutical compositions according to the invention can be topical, enteral or parenteral, preferably a oral administration, conjunctive, cutaneous, endotracheal, intradermal, intraepidermal, intramuscular, intravascular, laryngeal, nasal, ophthalmic, oral, rectal, respiratory, subcutaneous, transcutaneous or vaginal. It is generally It is advantageous to formulate such pharmaceutical compositions as a single dose.

Each dose then comprises a predetermined amount of the ingredient active, associated with the vehicle, excipients and / or suitable adjuvants, calculated in order to obtain a given therapeutic effect. As an example of a single dose that can be administered via an oral route, mention may be made of tablets, gelatin capsules, granules and oral solutions or suspensions. As an example of a single dose that can be administered via a topical route (especially for the local treatment of genital warts and external perianals), mention may be made of ovules, gels, creams, lotions, solutions and patches. Suitable formulations for the selected dosage forms are known and described in, for example, Remington, The Science and Practice of Pharmacy, 19th edition, 1995, Mack Publishing Company, and therefore, can be easily prepared by someone with experience in The technique. It is known that the dosage varies from one individual to another, depending on the nature and intensity of the disease, the route of administration selected, the weight, age and sex of the patient; consequently, effective dosages should be determined according to these parameters by the specialist in this matter. As an indication, effective dosages may vary between 1 and 500 mg daily. The object of the present invention is also the use of the compounds of formula (I) to treat or prevent an infection with the papillomavirus, preferably in humans.

The object of the present invention is also the use of the compounds of formula (I) to inhibit the replication of the papilloma virus, by inhibiting the formation of the E1 / E2 protein complex. The object of the present invention is furthermore the use of the compounds of formula (I) to prepare a drug intended to treat or prevent infection with the papilloma virus, preferably in humans. The object of the present invention is in particular the use of compounds of formula (I) to prepare a drug intended to treat or prevent infection by a low-risk papilloma virus, such as HPV6, HPV7, HPV1, HPV13, HPV32. , HPV34, HPV40, HPV42, HPV43, HPV44, HPV53, HPV54, HPV55, HPV57, HPV58, HPV74, HPV91. The object of the present invention is in particular the use of compounds of formula (I) to prepare a drug intended to treat or prevent an infection by HPV6 and / or HPV11. Thus, the object of the present invention is also the use of compounds of formula (I) to prepare a drug for treating or preventing injuries and diseases associated with infections by the papillomavirus. The object of the present invention is in particular, the use of the compounds of formula (I) to prepare a drug intended to treat and prevent anogenital warts, such as condylomata acuminata and flat condylomas, laryngeal papillomas, conjunctiva or buccal papillomas and other epithelial lesions such as recurrent respiratory papillomatosis and low-grade and high-grade intraepithelial neoplasms, bowenoid papulosis, warts (common wart, plantar wart, verruca mirmecia, superficial warts, flat wart ...), epidermodysplasia verruciforme, carcinomas, in particular, anogenital carcinomas, and all lesions that they are associated with the papilloma virus. The object of the present invention is in particular, the use of compounds of formula (I) to prepare a drug intended to treat or prevent anogenital warts, such as condylomata acuminata and flat condylomata, laryngeal papillomas, conjunctiva or buccal and other epithelial lesions, such as recurrent respiratory papillomatosis and low-grade intraepithelial neoplasms and all lesions that are associated with the papillomavirus. The compounds, objects of the present invention, can be prepared according to the various synthetic routes described hereinafter. The compounds where G2 represents the radical as defined at the beginning, it can be prepared in the following way.

When W represents an oxygen atom, the ester precursors of the compounds of formula (I) are obtained from the intermediates of the following formulas (II) and (III): in the formula (II), A, B and G1 t are as defined at the beginning. In formula (III), Ri, R2 and G, are as defined at the beginning and P represents a group that protects an acid function, such as a linear or branched (C1-C4) alkyl. In this case, the peptide coupling is carried out between the compounds (II) and (III), for example in the presence of DESI in a basic and apolar medium in order to lead to the compound of formula (IV): The compound (IV) can also be obtained in the following manner. The compound (III) is converted into the corresponding acid chloride of formula (V) by the action of thionyl chloride, for example, (V) wherein R2, G and P are as defined at the beginning and which are reacted in the compound (II). Then, the deprotection of the group -C02P of the compound of formula (IV) is carried out by hydrolysis, in order to obtain the compound of formula (I) where W represents an oxygen atom and R3 is as defined at the beginning. If necessary, the compound of formula (I) obtained after the termination of the deprotection step or in addition the compound of formula (IV), is reacted with a Lawesson reagent, so that the compound of formula (VI) can be obtained : which, after hydrolysis, corresponds to the case when W represents a sulfur atom in the formula (I). Lawesson's reagent can, for example, be [2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetan-2,4-disulfide (Lawesson et al., Bull. Soc. Chim Belg., 1978, 87, 229). In the case when G ^ represents a bond, the compounds of formula (II) can be obtained from the compounds of formula (VII): where B is as defined at the beginning. The compounds of formula (VII) are subjected to an aromatic nucleophilic substitution, in a basic and polar medium in the presence of the compounds (VIII) of the formula: wherein A is as defined at the beginning and d represents bond, and the compounds of formula (IX) are obtained: where A and B are as defined at the beginning. In the case when it represents a hydrocarbon chain as defined in formula (I), the compound of formula (X) is reacted: wherein A and d are as defined at the beginning and X represents a halogen atom, under basic and polar conditions, with a compound of formula (XI): wherein B is as defined at the beginning, and the compounds of formula (XII) are obtained: where A, B and d are as defined at the beginning; The compounds of the formulas (IX) and (XII) are placed in the presence of sodium nitrite in an acid medium and then reduced by a hydride, for example, lithium aluminum hydride (J Org. Chem. 1953, 18, 971, J. Org. Chem. 1954, 19, 1157, and J. Am. Chem. Soc. 1952, 74, 3192), in order to obtain the compounds of formula (II) as defined at the beginning. In the case when R2 represents a hydrogen or bromine atom, the compounds of formula (III) can be obtained according to the methods of the literature (J. Med. Chem. 1998, 41, 5219 or WO 0135900). In the case when R2 represents a chlorine atom, the compounds of formula (III) can be obtained by reacting sulfuryl chloride in an acidic medium with a precursor of formula (XIII): where R1 t G and P are as defined at the beginning. The compounds of the formulas (VII), (VIII), (X) and (XI) are either commercial compounds or compounds obtained according to the known methods of organic synthesis easily accessible and easily understood by someone skilled in the art. . In the preferred case when B is a phenyl substituted with a piperidine, the compounds of formula (I) can be prepared according to the following synthetic route. In the case when d represents a bond, the compounds of formula (II) can be obtained from the compounds of formula (XIV): where R5 is as defined at the beginning. The compounds of formula (XIV) are subjected to an aromatic nucleophilic substitution in a basic and polar medium in the presence of the compounds (VIII), and the compounds of the formula (XV) are obtained: where A and R5 are as defined at the beginning. The compounds of formula (XV) are reduced by tin chloride in a polar medium (Tet Lett, 1984, 25 (8), 839), and then reacted with a dibromoalkane, for example, dibromopentane in a basic medium and apolar (Bioorg, Med Chem. Lett, 1996, 6 (5), 563), leading to the compounds of formula (XVI): (XVI) where A and R5 are as defined at the beginning. In the case when d represents a hydrocarbon chain, as defined in formula (I), the compound of formula (X) is reacted under basic and polar conditions, with a compound of formula (XVII): wherein R5 is as defined at the beginning, and the compounds of formula (XVIII) are obtained: where A, G1 and R5 are as defined at the beginning. The compounds of formula (XVI) and (XVIII) are placed in the presence of sodium nitride in an acidic medium and then reduced by a hydride, for example, lithium aluminum hydride in order to obtain the compounds of formula ( II) as defined at the beginning.

In the particular case when A represents a substituted phenyl and d is a bond, the compounds of formula (I) can be prepared according to the following synthetic route. The compound of formula (XIX) is reacted: wherein B, G, Ry, R2 and P are as defined at the beginning and Y represents a halogen such as bromine or iodine or a triflate group, under basic conditions for coupling to palladium, with a compound of formula (XX): I I I I (XX) wherein C represents an aryl or a heterocycle substituted several forms, leading to the compound (XXI) of formula: where B, C, G, R2 and P are as defined at the beginning. Next, the compound (XXI) is reacted under basic saponification conditions in order to lead to the compound of general formula (I). The compounds where G2 represents the radical w, as defined at the beginning, can be prepared in the following manner. The compounds of formula (IX) or (XII), as described at the beginning, are reacted with a compound of formula (XXII): wherein R ^ R2, G and P are as defined at the outset, either directly in the presence of triphosgene, for example, or by the previous transformation of one of the precursors into carbamoyl chloride. And then a final hydrolysis is carried out. The compound (XXII) can be obtained from the compound (XXIII) of the formula: (XXI II) where R1? R2, G and P are as defined at the beginning, by reacting the compound (XXIII) in the presence of hexamethylenetetramine (HMTA) in an apolar solvent followed by acid treatment. The compounds where G2 represents the radical, as defined at the beginning, it can also be prepared in the following way. When W represents an oxygen atom, the ester precursors of the compounds of formula (I) are obtained from the following intermediates of formulas (XXIV) and (V): In the formula (XXIV), A, B and G-i, are as defined at the beginning. In formula (V), R ^ R2 and G are as defined at the beginning and P represents a group protecting an acid function, such as a straight or branched C1-C4 alkyl. In this case, the compound (V) is reacted with in the compound (XXIV) in an acidic medium in order to lead to the compound of the formula (IV): Next, the deprotection of the group -CO 2 P of the compound of the formula IV) is carried out by hydrolysis, in order to obtain the compound of formula (I): where W represents an oxygen atom and R3 is as defined at the beginning. In the preferred case, when B is a phenyl substituted with a piperidine and when d represents a bond, the compounds of formula (XXIV) can be obtained from the compounds of formula (XIV): where R5 is as defined at the beginning.

The compounds of formula (XIV) are subjected to an aromatic nucleophilic substitution in a polar medium in the presence of commercial Boc-hydrazine, and the compounds of formula (XXV) are obtained: where R5 is as defined at the beginning. The compound of formula (XXV) is placed in the presence of manganese oxide (Org. Letters, 2006, 8, 1, 43), and then subjected to an N-arylation reaction leading to the compounds of formula (XXVI) : where A and R5 are as defined at the beginning. The compounds of formula (XXVI) are reduced by catalytic hydrogenation, and when they are reacted with a dibromoalkane or an acid chloride, for example, 5-bromovaleryl chloride in a basic and apolar medium, and then cyclized in a medium basic and polar such as by sodium hydride in dimethylformamide and finally borane reduced, in order to lead to the compound of formula (XXVII): where A and R5 are as defined at the beginning.

The object of the present invention is also the synthesis of the intermediates corresponding to the compounds (II) grouped in Table (II).

TABLE II to N- (4-methoxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine b N- (2-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxy-phenyl) -hydrazine c N- (3-methoxy-benzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine d N- (4-benzyloxy-phenyl) -N- (2-piperidin-1-yl- phenyl) -hydrazine and N- [4- (4-fluoro-phenoxy) -phenyl] -N- (2-piperidin-1-yl-phenyl) -hydrazine f N- [2- (4-methoxy-phenyl) - ethyl] -N- (2-piperidin-1-yl-phenyl) -hydrazine g N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine H N - (4-methoxy-benzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine i N- (4-cyclohexyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine j N- (2-methyl-6-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxy-phenyl) -hydrazine k N- (4'-methoxy-biphenyl-4-yl) -N- (2 -piperidin-1-yl-phenyl) -hydrazine I N- (4-cyclohexyloxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine m N- (4-phenoxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine n N- [4- (4-chloro-phenoxy) -phenyl] -N- (2-piperidin-1-yl-phenyl) -hydrazine 0 N- [4 - (4-Fluoro-phenoxy) -phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine P N- (4-benzyl-phenyl] -N- (2-piperidin-1-yl-phenyl) -hydrazine q N- (4-bromo-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine G N- (3-phenoxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine s N- (4-phenylsulfanyl-phenyl) -N- (2-piperidin-1-yl- phenyl) -hydrazine t N- (4-benzyl-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine or N- (4'-methoxy-biphenyl-4-yl) - N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine V N- (4-benzoyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine w N- [4 '- (2-methyl- [1, 3] dithian-2-yl) -biphenyl-4-yl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine X N- (4 '-methoxy-2-methyl-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine The following examples illustrate the invention, but do not limit it by any of its meanings.

The starting products used are commercial products or products prepared according to known operating procedures from commercial products or known by someone with experience in the technique. The different preparations lead to the synthesis of the intermediates useful for preparing the compounds of the invention.

The structures of the compounds described in the examples and the preparations were determined according to the techniques usual spectrometry (nuclear magnetic resonance (NMR), Mass spectrometry (MS), including electro-vacuum (ES), melting point (MP) ...), and the purity was determined by high performance liquid chromatography performance (HPLC) and was confirmed by elemental analysis.

Abbreviations used in the operation procedures: • AIBN: 2,2'-azobis (2-methylpropionitrile) • TLC: thin layer chromatography • EDCI: 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride • DMAP: 4-dimethylaminopyridine • DMSO: dimethyl sulfoxide • DIPEA:?,? - diisopropylethylamine • HOBt: 1-hydroxybenzotriazole • TFA: trifluoroacetic acid Preparation 1: Methyl 4-carboxymethyl-2-methoxybenzoate Methyl 4-carboxymethyl-2-methoxybenzoate can be prepared according to the method described in J. Med. Chem. 1998, 41, 5219 or in WO 0135900 .

Preparation 2: Methyl 5-bromo-4-carboxymethyl-2-methoxybenzoate Methyl 5-bromo-4-carboxylmethyl-2-methoxybenzoate is obtained from preparation 1, according to the procedure described in WO 0135900.

Preparation 3: Methyl 5-chloro-4-carboxymethyl-2-methoxy-benzoate 300 mg of methyl 4-carboxymethyl-2-methoxy-benzoate from preparation 1 were placed in 6 mL of acetic acid, 110 pL was added of sulfuryl chloride (1 equivalent). All was refluxed for 6 hours. After evaporation of the solvent, the crude reaction product was purified on silica gel (petroleum ether / ethyl acetate: 80/20, then 60/40), yielding 165 mg of the desired compound. Yield: 47% HPLC: 96% MS: MH + 259/261.

Preparation 4: 4 - ((E) -2-carboxy-vinyl) -2-methoxy-benzoate methyl Stage 1: 4 Methyl bromomethyl-2-methoxy-benzoate To 5.38 g of 2-methoxy-4-methyl-benzoate of methyl in 20 ml_ of carbon tetrachloride was added 5.3 g of N-bromosuccinimide (1 equivalent) and 490 mg of AIBN (0.1 equivalent) away from direct light. All was refluxed by heating overnight. The reaction medium was evaporated under reduced pressure and then purified on silica gel (petroleum ether / ethyl acetate: 90/10), yielding 3.73 g of the desired product. Yield: 48% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.76 (d, 1 H), 6.99 (m, 2H), 4. 46 (s, 2H), 3.92 (s, 3H), 3.88 (s, 3H). HPLC: 96% MS: MH + 259/261.

Step 2: Methyl 4-hydroxymethyl-2-methoxybenzoate To 1.5 g of the product obtained in the previous step in 25 ml_ of dioxane, a suspension of 2.55 g (4.4 equivalents) of calcium carbonate in 25 ml of Water. Everything was heated for 6 hours at 100 ° C. After evaporation of the reaction medium, the crude product was taken up in dichloromethane, acidified with a 1N hydrochloric acid solution. The reaction medium was extracted several times with dichloromethane, the organic phases were collected and then dried over sulphate. of magnesium were filtered and evaporated under reduced pressure, leading to 1.0 g of the desired product. Yield: 96% 1 H NMR (CDC, 300 MHz) d (ppm): 7.78 (d, 1 H), 7.01 (m, 1 H), 6.93 (d, 1 H), 4.73 (s, 2 H), 3.91 ( s, 3H), 3.88 (s, 3H).

Step 3: Methyl 4-formyl-2-methoxybenzoate To 1.10 g of the product obtained in the previous step in 20 mL of dioxane, 4.87 g of activated manganese oxide (10 equivalents) was added. Everything was stirred at room temperature for 24 hours, and then filtered over celite. The filtrate was evaporated under reduced pressure and the residue obtained was purified by chromatography on silica gel (petroleum ether / ethyl acetate: 90/10, and then 80/20), yielding 540 mg of the desired product. Yield: 50% 1 H NMR (CDC, 300 MHz) d (ppm): 10.02 (s, 1 H), 7.89 (d, 1 H), 7.48 (m, 2 H), 3.97 (s, 3 H), 3.92 (s) , 3H).

Step 4: 4 - ((E) -2-tert-butoxycarbonyl-vinyl) -2-methoxy-benzoic acid methyl ester To 720 pL of tert-butyl diethylphosphonoacetate (1.1 equivalents) in 3 mL of tetrahydrofuran cooled to 0 ° C under an inert atmosphere, 307 mg of sodium tert-butanolate (1.15 equivalents) were added. All was stirred for 30 minutes at 0 ° C and then for 1 hour at room temperature. A solution cooled to 0-4 ° C of 540 mg of the aldehyde obtained in step 3 in 1 ml of tetrahydrofuran was added dropwise to the premix also cooled to 0 ° C. Stirring was maintained at this temperature for 30 minutes before allowing the temperature to rise again at room temperature for 2 hours. The medium was hydrolyzed with a saturated solution of ammonium chloride and extracted with ethyl acetate several times. The collected organic phases were washed with water, and then dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude reaction product was purified by chromatography on silica gel (petroleum ether / ethyl acetate: 95/5), yielding 500 mg of the expected product. Yield: 61% 1 H NMR (DMSO, 300 MHz) d (ppm): 7.48-7.66 (aromatic mass, 3H), 6.70 (d, 1 H), 3.87 (s, 3H), 3.79 (s, 3H), 1.49 (s, 9H) HPLC: 93% MS: MH + 293.

Step 5: 4 - Methyl ((E) -2-carboxy-vinyl) -2-methoxybenzoate To 100 mg of the diester obtained in the previous step in 1.6 mL of dichloromethane, 0.8 mL of trifluoroacetic acid was added. The whole was stirred for one hour at room temperature and then evaporated under reduced pressure with a mixture of toluene and dichloromethane as cosolvents. Yield: 99% 1 H NMR (DMSO, 300 MHz) d (ppm): 7.57-7.67 (m, 2H), 7.47 (s, 1 H), 7.32 (d, 1 H), 6.67 (d, 1 H), 3.87 (s, 3H), 3.79 (s, 3H) HPLC: 90%.

Preparation 5: Methyl 5-bromo-4 - ((E) -2-carboxy-vinyl) -2-methoxy-benzoate Stage 1: Methyl 5-bromo-4-bromomethyl-2-methoxy-benzoate To 2.5 g of Methyl 2-methoxy-4-methylbenzoate in 15 mL of acetic acid, 550 pL of bromine (1.1 equivalents) was added dropwise at room temperature. Everything was stirred overnight, until the complete disappearance of the initial product (tracked by TLC). The reaction medium was hydrolyzed by a 1 N sodium hydroxide solution, extracted with ethyl acetate. The organic phases were dried over magnesium sulfate and then concentrated under reduced pressure, leading to 2.72 g of a pale yellow oil, which was crystallized. Yield: 83% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.98 (s, 1 H), 7.06 (s, 1 H), 4.55 (s, 2 H), 3.92 (s, 3 H), 3.89 (s) , 3H) HPLC: 85% MS: MH + 336/338/340.

Stage 2: Methyl 5-bromo-4-hydroxymethyl-2-methoxybenzoate The product (880 mg) is obtained according to the method of step 2 of preparation 4 from 1.3 g of the product from the previous stage in the presence of 1.7 g of calcium carbonate. Yield: 83% H NMR (CDCl 3, 300 MHz) d (ppm): 7.96 (s, 1 H), 7.20 (s, 1 H), 4.75 (s, 2 H), 3.92 (s, 3 H), 3.88 (s) , 3H) HPLC: 96% MS: MH + 275/277.

Step 3: Methyl 5-bromo-4-formyl-2-methoxybenzoate The product (725 mg) is obtained according to the method of step 3 of preparation 4, using 875 mg of the previous alcohol in the presence of 2.8 g of activated manganese oxide. Yield: 83% 1 H NMR (CDC, 300 MHz) d (ppm): 10.33 (s, 1 H), 8.01 (s, 1 H), 7.49 (s, 1 H), 3.95 (s, 3 H), 3.92 ( s, 3H) HPLC: 96% MS: MH + 273/275.

Step 4: Methyl 5-bromo-4 - ((E) -2-tert-butoxycarbonylvinyl) -2-methoxybenzoate The product (860 mg) is obtained according to the method of step 4 of preparation 4, using 725 mg of the previous aldehyde in the presence of 688 μl of tert-butyl diethylphosphonoacetate and 293 mg of sodium tert-butanolate. Estimated yield: 87% 1 H NMR (CDCb, 300 MHz) d (ppm): 8.00 (s, 1 H), 7.89 (d, 1 H), 7.13 (s, 1 H), 6.34 (d, 1 H), 3.92 (s, 3H), 3.89 (s, 3H), 1.55 (s, 9H) HPLC: 63% MS: MH + 371/373 Step 5: Methyl 5-bromo-4 - ((E) -2-carboxy-vinyl) -2-methoxybenzoate The product (489 mg) is obtained according to the method of step 5 of preparation 4, using 860 mg of the previous cinnamic ester in the presence of 5 ml_ of trifluoroacetic acid. Yield: 67% 1 H NMR (DMSO, 300 MHz) d (ppm): 7.88 (s, 1 H), 7.75 (d, 1 H), .57 (s, 1 H), 6.83 (d, 1 H), 3.90 (s, 3H), 3.80 (s, 3H) HPLC: 89% MS: MH + 315/317.

EXAMPLE 1 5-Bromo-2-methoxy-4-fN- (4-methoxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-benzoic acid hydrochloride (1) Step 1: (4-methoxy-phenyl) - (2-nitro phenyl) -amine To 3.7 mL of 2-fluoro-nitrobenzene was added 8.73 g of 4-methoxyaniline (2 equivalents). Everything was heated at 1 0 ° C overnight. The medium was taken up in ethyl acetate, washed successively with water, a saturated solution of sodium bicarbonate and then with a saturated solution of sodium chloride. The organic phase was dried over magnesium sulfate, filtered and then concentrated under reduced pressure. With chromatography on silica gel of the residue (petroleum ether / ethyl acetate: 90/10), 8.63 g of the desired product were isolated. Yield: 99% 1 H NMR (DMSO, 300 MHz) d (ppm): 9.35 (s, 1 H), 8.10 (d, 1 H), 7.45 (t, 1 H), 7.25 (d, 2H), 6.98 ( m, 3H), 6.79 (t, 1 H), 3.78 (s, 3H) HPLC: 100%.

Step 2: N- (4-methoxy-phenyl) benzene-1,2-diamine To a solution of 4 g of the product obtained in the previous step in 80 mL of ethanol was added 18.5 g of tin chloride hydrate ( 5 equivalents). All was refluxed for 5 hours and then stirred at room temperature overnight. The medium was hydrolyzed under cold conditions, adjusted to a pH of 8 with a saturated solution of sodium bicarbonate and extracted with ethyl acetate several times. The collected organic phases were dried over magnesium sulfate, filtered and evaporated in vacuo. The obtained residue was purified by chromatography on silica gel (toluene and then toluene / ethyl acetate: 95/5), yielding 2.9 g of the expected product. Yield: 82% 1 H NMR (DMSO, 300 MHz) d (ppm): 6.89 (d, 1 H), 6.75 (m, 7 H), 6.50 (t, 1 H), 4.67 (s, 2 H), 3.67 (s) , 3H) HPLC: 100%.

Step 3: (4-methoxy-phenyl) - (2-piperidin-1-yl-phenyl) -amine To a solution of 2.5 g of the aniline obtained initially in 15 mL of toluene, 2.47 g of succinate were added in succession. sodium carbonate (2 equivalents) and 1.6 mL of dibromopentane (1 equivalent). Everything was refluxed for 24 hours. After returning to room temperature, the sodium carbonate was removed by filtration and rinsed with dichloromethane. The filtrate was evaporated under reduced pressure. The residue obtained was purified by chromatography on silica gel (petroleum ether, petroleum ether / ethyl acetate: 98/2), yielding 1.72 g of the desired product. Yield: 52% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.10 (m, 4H), 6.92 (m, 3H), 6. 78 (m, 1 H), 6.52 (s, 1 H), 3.81 (s, 3H), 2.86 (m, 4H), 1.71 (m, 4H), 1.60 (m, 2H) HPLC: 100%.

Step 4: N- (4-methoxy phenyl) -N- (2-piperidin-1-phenyl) -hydrazine (a) 806 mg of the product obtained in the previous step, were solubilized in 10 mL of acetic acid. To this solution cooled between 5 and 15 ° C, a solution of 1.14 g of sodium nitride in 3 mL of water (5.8 equivalents) was added dropwise. After 10 minutes of stirring, ice was added to the reaction medium, the formed precipitate was filtered, washed with water and then dried in vacuo. A brown powder corresponding to the nitroso intermediate was obtained (followed by TLC and NMR). This unpurified intermediate, taken in 8 mL of diethyl ether, was cooled directly to 10 ° C. To this solution was added a suspension of 1 19 mg of lithium aluminum hydride (1.1 equivalents) in 2 mL of diethyl ether. Everything was stirred for 1 hour until the complete disappearance of the starting product (tracked by TLC). The reaction medium was poured into a 1 N sodium hydroxide solution and extracted several times with diethyl ether. The organic phase was dried, filtered and evaporated under reduced pressure, leading to a residue which was purified by chromatography (petroleum ether / ethyl acetate: 95/5). 382 mg of the product corresponding to hydrazine was obtained as a rose oil. Yield: 45% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.08 (m, 5H), 6.95 (m, 1 H), 6.81 (m, 2H), 3.78 (s, 3H), 3.04 (m, 4H), 1.73 (m, 4H), 1.57 (m, 2H).

Step 5: Methyl 5-bromo-2-methoxy-4-fN- (4-methoxyphenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-1-benzoate To a solution of 367 mg of the previous compound in 10 mL of dichloromethane, 412 mg of the acid of preparation 2 (1.1 equivalents), 260 mg of EDCI (1.1 equivalents) and 45 mg of DMAP (0.3 equivalents) were added. The reaction medium was stirred at room temperature, and heated if necessary, until complete disappearance of the starting hydrazine (time> 15 hours), and then hydrolyzed and extracted with dichloromethane several times. The organic phases were washed with a 1N sodium hydroxide solution and then with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue obtained was purified by chromatography on silica gel (petroleum ether / ethyl acetate: 72/25, and then 70/30), yielding 546 mg of the expected product.

Yield: 76% 1 H NMR (DMSO, 300 MHz) d (ppm): 10.65 (s, 1 H), 7.81 (s, 1 H), 7.30 (m, 2 H), 6.99 (m, 4 H), 6.72 (m , 4H), 3.79 (broad 2s, 8H), 3.69 (s, 3H), 2.50 (broad s, 4H), 1.12 (m, 6H) HPLC: 96%.

Step 6: 5-Bromo-2-methoxy-4- [N- (4-methoxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine-carbonyl-methyl-benzoic acid hydrochloride (1) A a solution of 100 mg of the product obtained in step 5, in 2 mL of dioxane, was added 343 [mu] l of a 1N sodium hydroxide solution (2 equivalents). The reaction medium was stirred at room temperature for 4 hours and then concentrated under reduced pressure. The solid obtained was taken in a minimum amount of water and acidified with a 1 N hydrochloric acid solution to a pH of 1. In the present case, extraction with dichloromethane allowed the crude reaction product to be isolated. After evaporation, the residue was taken up in ether. A precipitate was formed, which was filtered and washed leading to 52 mg of the expected product as a hydrochloride. Yield: 50% P.f .: 109 ° C (decomposition) Elemental analysis calculated for C28H30BrN3O5. I HCI I .5H2O: C, 53.22; H, 5.42; N, 6.65. Found: C, 52.84; H, 5.08; N, 6.24.

HPLC: 97% MS: MH + 568/570.

EXAMPLE 2 5-Bromo-2-methoxy-4- [N- (2-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxy-phenhydro-dinocarbonylmethyl-benzoic acid) hydrochloride (2) Step 1: (2-Nitro-phenyl) - (4-trifluoromethoxy-phenyl) -amine To 374 μl of the 2-fluoro-nitrobenzene in 2 ml of DMSO, 962 μl of 4-trifluoromethoxyaniline (2 equivalents) and 636 mg of potassium tert-butanolate (1.6 equivalents). Everything was heated to 1 10 ° C for 3 hours. Once the reaction was finished, the medium was taken in a minimum amount of dichloromethane, hydrolyzed and then extracted. The organic phase was washed successively with water and then with a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure. Chromatography on silica gel of the residue (cyclohexane and then cyclohexane / ethyl acetate: 99/1) allowed 575 mg of the desired product to be isolated. Yield: 54% H NMR (CDCl 3, 300 MHz) d (ppm): 9.43 (s, 1 H), 8.22 (d, 1 H), 7. 43 (t, 1 H), 7.25-7.38 (m, 4H), 7.19 (d, 1 H), 6.83 (t, 3H) HPLC: 97% MS: MH + 299.

Step 2: N- (4-Trifluoromethoxy phenyl) -benzene-1,2-diamine The product (600 mg) is obtained according to the method of step 2 of Example 1, using 570 mg of the previous derivative as an initial product and 2.16 g of tin chloride hydrate in 10 ml_ of ethanol. Yield: quantitative 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.01 -7.12 (m, 4 H), 6.73-6.86 (m, 2 H), 6.70 (m, 2 H), 5.30 (broad s, 1 H) HPLC : 96% MS: MH + 269.

Step 3: (2-Piperidin-1-yl-phenyl) - (4-trifluoromethoxy-phenyl) -amine The product (350 mg) is obtained according to the method of step 3 of Example 1, using 513 mg of the previous aniline as a substrate and 261 μg of dibromopentane in the presence of 405 mg of sodium carbonate in 5 ml of toluene. Yield: 54% 1 H NMR (CDC, 300 MHz) d (ppm): 7.28 (m, 2H), 7.13 (s, 3H), 7.09 (d, 1 H), 7.01 (t, 1 H), 6.88 (t , 1 H), 6.70 (s, 1 H), 2.83 (m, 4H), 1.71 (m, 4H), 1.59 (m, 2H).

Step 4: N- (2-Piperidin-1-yl-phenyl) -N- (4-trifluoromethoxyphenyl) -hydrazine (b) The product (180 mg) is obtained according to the method of step 4 of Example 1, using 345 mg of the previous derivative as an initial product and 410 mg of sodium nitrite in 4 ml_ of acetic acid, leading to the nitrous intermediate which was reduced with 28 mg of lithium aluminum hydride in 4 ml_ of diethyl ether. Yield: 50% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.04-7.22 (aromatic mass, 8H), 3.09 (m, 4H), 1.83 (m, 4H), 1.59 (m, 2H) MS: MH + 352 Stage 5: Methyl 5-bromo-2-methoxy-4- (N- (2-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxypheniD-hydrazinocarbonylmethylbenzoate) The product (250 mg) is obtained in accordance with the method of step 5 of Example 1, using 176 mg of the preceding hydrazine as a substrate and 167 mg of the acid of preparation 2 as a co-substrate in the presence of 106 mg of EDCI and 18 mg of DMAP. % H NMR (CDCl 3, 300 MHz) d (ppm): 9.32 and 9.35 (2s in proportions of 70/30, 1 H), 7.93 and 7.99 (2s in proportions of 30/70, 1 H), 6.74-7.50 ( m, 9H), 3.70-4.07 (3s, 8H), 2.67 (m, 4H), 1 .43-1 .56 (m, 6H) HPLC: 98% MS: MH + 636/638.

Step 6: 5-Bromo-2-methoxy-4-fN- (2-piperidin-1-phenyl) -N- (4-trifluorom (2)) Hydrochloride To a solution of 100 mg of the product obtained in Stage 5 in 2 mL of dioxane, was added 1.6 mL of a 1 N sodium hydroxide solution (10 equivalents) The reaction medium was stirred at room temperature for 4 hours and then concentrated under reduced pressure. in a minimum amount of water and acidified with a 1 N hydrochloric acid solution to a pH of 1. A precipitate formed, which was filtered, taken up in ether and washed leading to 52 mg of the expected product as a hydrochloride Yield: 69% P.f .: 157 ° C (decomposition) Elemental analysis calculated for C28H27BrF3N3O5 I HCl I H2O: C, 49.68; H, 4.47; N, 6.21 Found: C, 50.01; H, 4.62; N, 5.91 HPLC: 98% MS: MH + 622/624.

EXAMPLE 3 5-Bromo-2-methoxy-4-rN- (3-methoxy-benzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-1-benzoic acid hydrochloride (3) Step 1: (3-methoxy-benzyl) - (2-piperidin-1-yl-phenyl) -amine To 1 g of 2-p'iperidinoanilina in 10 mL of DMF was added 795 μ? _ Of bromide of 3- methoxybenzyl (1 equivalent) and 1.57 g of potassium carbonate (2 equivalents). Everything was heated at 100 ° C for 2-3 hours, until the disappearance of the starting aniline. The medium was poured onto ice and then extracted with ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate, filtered and evaporated under reduced pressure. By chromatography on silica gel of the residue (cyclohexane / ethyl acetate: 99/1), 1.46 g of the desired product can be isolated. Yield: 87% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.26 (m, 1 H), 6.99 (m, 4 H), 6.81 (d, 1 H), 6.68 (t, 1 H), 6.57 ( d, 1 H), 4.35 (s, 2 H), 3.80 (s, 3 H), 2.86 (s broad, 4 H), 1.69 (s broad, 6 H) HPLC: 97% MS: MH + 297.

Step 2: N- (3-Methoxy-benzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine (c) According to the method of step 4 of Example 1, the nitroso intermediate (376 mg) is obtained by extraction with ethyl acetate of the quenched reaction medium to pH 7 using 353 mg of the previous derivative as a starting product, and 477 mg of sodium nitrite in 3 ml_ of acetic acid. A suspension of 180 mg of lithium aluminum hydride (4 equivalents) in 5 ml_ of diethyl ether was applied to this intermediate for 2 hours with reflux, leading to 138 mg of hydrazine after purification. Yield: 37% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.26 (m, 1 H), 6.91 -7.1 1 (aromatic mass, 6H), 6.80 (dd, 1 H), 4.56 (s, 2H) , 3.80 (s, 3H), 3.12 (m, 4H), 1 .59-1.79 (m, 6H).

Stage 3: Methyl 5-bromo-2-methoxy-4- [N- (3-methoxybenzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonyl-methyl-1-benzoate The product (183 mg) obtained according to the method of step 5 of Example 1, using 137 mg of the pre-hydrazine as a substrate and 160 mg of the acid of preparation 2 as a co-substrate in the presence of 101 mg of EDCI and 16 mg of DMAP. Yield: 70% HPLC: 100% MS: MH + 596/598.

Step 4: 5-Bromo-2-methoxy-4-fN- (3-methoxybenzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-benzoic acid hydrochloride (3) The product (152 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 82% P.f .: 109-1 12 ° C Elemental analysis calculated for C29H32BrN3O5.1 HCl.1.5H2O: C, 53.92; H, 5.62; N, 6.50. Found: C, 54.08; H, 5.67; N, 5.79. HPLC: 100% MS: Mhf 582/584.

EXAMPLE 4 4- [N- (4-Benzyloxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethin-5-bromo-2-methoxybenzoic acid hydrochloride (4) Step 1: (4-Benzyloxy-phenyl) - (2-nitro-phenyl) -amine To 600 μl of 2-fluoro-nitrobenzene, 6 ml of DMSO, 1.7 g of 4- (benzyloxy) aniline were added ( 1.5 equivalents) and 1.02 g of potassium tert-butanolate (1.6 equivalents). All was heated at 1 10 ° C for 1 hour 30. The medium was then hydrolyzed and extracted several times with ethyl acetate. The organic phases were washed with a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and then concentrated under reduced pressure. Chromatography on silica gel of the residue (cyclohexane / ethyl acetate: 99/1) allowed 754 mg of the desired product to be isolated. Yield: 41% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 9.40 (broad s, 1 H), 8.18 (d, 1 H), 7.23-7.45 (m, 6H), 7.17-7.21 (m, 2H ), 7.05 (m, 3H), 6.71 (t, 1 H), 5.09 (s, 2H) MS: MH + 321.

Step 2: N- (4-Benzyloxy-phenyl) -benzene-1-l2-diamine The product (653 mg) is obtained according to the method of step 2 of Example 1, using 754 mg of the previous derivative as an initial product and 2.66 g of tin chloride hydrate in 12 mL of ethanol. Yield: 95% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.68-7.37 (aromatic mass, 13H), 5.01 (s, 2H) HPLC: 82% MS: Mhf 291.

Step 3: (4-benzyloxy-phenyl) - (2-piperidin-1-yl-phenyl) -amine To a solution of 653 mg of the aniline previously obtained in 4 mL of toluene, 940 pL of DIPEA was successively added. (2.4 equivalents) and 305 pL of dibromopentane (1 equivalent). All was refluxed for 2 hours until the complete disappearance of the starting aniline. After returning to room temperature, the reaction medium was hydrolyzed and extracted several times with ethyl acetate. The organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The obtained residue was purified by chromatography on silica gel (cyclohexane and then cyclohexane / ethyl acetate: 99.5 / 0.5), yielding 480 mg of the desired product. Yield: 60% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.31-7.41 (m, 5H), 7.05-7.15 (m, 4H), 6.95 (m, 3H), 6.78 (t, 3H), 6.53 (s broad, 1 H), 5.06 (s, 2H) HPLC: 94% MS: MH + 359.

Step 4: N- (4-benzyloxyphenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine (d) The product (202 mg) is obtained according to the method of step 4 of Example 1, using 488 mg of the previous derivative as a starting product, and 545 mg of sodium nitrite in 5 ml_ of acetic acid, leading to the nitrous intermediate, which was reduced by 74 mg of lithium aluminum hydride (2 equivalents) in 5 ml_ of diethyl ether. Yield: 40% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.73-7.40 (aromatic mass, 3H), 4.94 (s, 2H), 2.90 (m, 4H), 1.61 (m, 4H), 1.43 and 1.50 (m, 2H) Step 5: 4- [N- (4-benzyloxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonyl-methylene-5-bromo-2-methoxy- Methyl benzoate The product (193 mg) is obtained according to the method of step 5 of Example 1, using 202 mg of the previous hydrazine as a substrate and 180 mg of the acid of preparation 2 as a co-substrate in the presence of 1 14 mg of EDCI and 20 mg of DMAP. Yield: 54% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 9.37 (broad s, 1 H), 7.98 (d, 1 H), 7.30-7.37 (m, 5H), 7.05-7.30 (m, 2H ), 6.70-6.84 (m, 5H), 4.99 (d, 2H), 3.68-4.08 (3s, 8H), 2.66 (m, 4H), 1.43-1.63 (m, 6H).

Step 6: 4- [N- (4-benzyloxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-5-bromo-2-methoxybenzoic acid hydrochloride (4) The product is obtained according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. With purification by reverse phase chromatography (conditions: column C18, 21.2 x 150 mm, half-Socratic 30% acetonitrile / H20 + 0.05% TFA, flow rate: 15 mL / minute, wavelengths: 220 and 254 nm), followed by treatment with a 1N hydrochloric acid solution, the desired product can be isolated as a hydrochloride (40 mg). Yield: 21% P.f .: 1 14 ° C HPLC: 98% MS: Mhf 644/646.

EXAMPLE 5 5-Bromo-4-N-f4- (4-fluoro-phenoxy) -phenin-N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl) -2-methoxy-benzoic acid hydrochloride (5) Step 1: 1-Nitro-4- (4-fluoro-phenoxy) -benzene To a solution of 1.5 mL of 4-fluoronitrobenzene in 28 mL of dimethylformamide was added successively 1.75 g of 4-fluoronitrobenzene (1.1 equivalents) and 2.15 g of potassium carbonate (1.1 equivalents). All was heated at 150 ° C for 4 hours 30. After returning to room temperature, the medium was poured on ice and placed under stirring for 30 minutes. A precipitate formed, which was filtered, rinsed with water and then dried (3.02 g). Yield: 91% 1 H NMR (CDCl 3, 300 Hz) d (ppm) 8.20 (d, 2 H), 6.97-7.16 (aromatic mass, 6 H).

Step 2: 4- (4-fluoro-phenoxy) phenylamine To a solution of 3.02 of the product obtained in the previous step in 50 mL of ethanol was added 14.6 g of tin chloride hydrate (5 equivalents). All was refluxed for 1 hour. After returning to room temperature, the medium was poured onto ice, basified to a pH of 10 by means of a 4 N sodium hydroxide solution and extracted with ethyl acetate several times. The collected organic phases were dried over magnesium sulfate, filtered and evaporated under reduced pressure, yielding 2.6 g of the expected product. Yield: quantitative 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.82-7.03 (aromatic mass, 6H), 6.71-6.79 (m, 2H) MS: MH + 204.

Step 3: [4- (4-Fluoro-phenoxy) -phenyl- (2-nitro-phenyl) -amine The product (790 mg) is obtained according to the method of step 1 of Example 4, using 900 μ? of 2-fluoro-nitrobenzene and 2.6 g of the product obtained in the previous step in the presence of 1.53 g of potassium tert-butanolate in 9 ml of DMSO. Yield: 28% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 9.46 (broad s, 1 H), 8.25 (d, 1 H), 7.42 (t, 1 H), 7.28 (m, 2H), 7.05 -7.19 (aromatic mass, 7H), 6.77 (t, 1 H) HPLC: 92% MS: MH + 325.

Step 4: N- [4- (4-Fluoro-phenoxy) -phenill-benzene-1-l2-diamine The product (637 mg) is obtained according to the method of step 2 of Example 1, using 750 mg of the derivative previous as an initial product and 2.61 g of tin chloride hydrate in 12 mL of ethanol. Yield: 93% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.17-7.13 (aromatic mass, 12H) HPLC. 92% MS: MH + 295.

Step 5: [4- (4-Fluoro-phenoxy) -phenyl- (2-piperidin-1-yl-phenyl) -amine The product (715 mg) is obtained according to the method of step 3 of Example 4, using 635 mg of the previous derivative as a starting product, 294 μ? of dibromopentane and 905 pL of DIPEA in 4 mL of toluene. Yield: 91% H NMR (CDCl 3, 300 MHz) d (ppm): 6.79-7.26 (aromatic mass, 12H), 6.63 (broad s, 1 H), 2.84 (m, 4H), 1.74 (m, 4H), 1.60 (m, 2H) HPLC: 98% MS: MH + 363.

Step 6: N-f4- (4-fluoro-phenoxy) -phenyl-N- (2-piperidin-1-yl-phenyl) -hydrazine (e) The product (275 mg) was obtained according to the method of step 4 of Example 1, using 715 mg of the previous derivative as an initial product and 791 mg of sodium nitrite in 7 mL of acetic acid, leading to the nitroso intermediate, which was reduced by 150 mg of lithium aluminum hydride (2 equivalents) ) in 7 mL of diethyl ether. Yield: 37% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.83-7.19 (aromatic mass, 12H), 3.00 (m, 4H), 1.73 (m, 4H), 1.58 (m, 2H).

Step 7: 5-Bromo-4- (N- [4- (4-fluoro-phenoxy) -phenyl-N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl) -2-methoxy-benzoate methyl product (336 mg) is obtained according to the method of step 5 of Example 1, using 275 mg of the previous hydrazine as a substrate and 243 mg of the acid of preparation 2 as a co-substrate in the presence of 154 mg of EDCI and 27 mg of DMAP. Yield: 69% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 9.35 (broad s, 1 H), 7.98 (d, 1 H), 6.73-7.50 (aromatic mass, 13H), 3.69-4.13 (3s, 8H), 2.72 (m, 4H), 1 .46-1.60 (m, 6H) HPLC: 95% MS: MH + 662/664.

Step 8: 5-Bromo-4- (N-f4- (4-fluoro-phenoxy-phenyl-N- (2-piperidin-1-phenyl) -hydrazine ^ (5) Hydrochloride The product is obtained in accordance with the method of step 6 of Example 2, using as a substrate the product obtained in the previous step With the purification by reverse phase chromatography of a fraction (conditions: column C18, 21.2 x 150 mm, isocratic medium 30% acetonitrile / H20 + 0.05% TFA, flow rate: 15 mL / minute, wavelengths 220 and 254 nm), followed by treatment with a 1 N hydrochloric acid solution, the expected product could be isolated as a hydrochloride (43 mg) Estimated yield: 44% P.f .: 224-231 ° C Elemental analysis calculated for C33H31BrFN305.1 HCI.1 H20: C, 56.38; H, 4.88; N, 5.98 Found: C, 56.28; H, 4.91; N, 5.78, HPLC: 98% MS: MH + 648/650.

EXAMPLE 6 5-Bromo-2-methoxy-4-N-r2- (4-methoxyphenyl) -etill-N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl) -benzoic acid hydrochloride (6) Step 1: f2- (4-Methoxy-phenyl) -etill- (2-piperidin-1-yl-phenyl) -amine To 1 g of 2-piperidinoaniline in 10 mL of DMF, 1.72 mL of sodium chloride was added. 4-methoxyphenethyl (2 equivalents) and 2.35 g of potassium carbonate (3 equivalents). All was heated at 100 ° C for 60 hours and then poured onto ice and extracted with ethyl acetate. The organic phase was washed with a saturated solution of sodium chloride, dried over magnesium sulfate, filtered and evaporated under reduced pressure. With several chromatographies on silica gel of the residue (petroleum ether, petroleum ether / ethyl acetate: 98/2), 255 mg of the desired product could be isolated. Yield: 14% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.17 (d, 2H), 6.99 (m, 2H), 6.86 (m, 2H), 6.66 (m, 2H), 4.77 (s broad, 1 H), 3.80 (s, 3H), 3.36 (t, 2H), 2.90 (t, 2H), 2.72 (broad s, 4H), 1.57 (m, 6H).

Step 2: N-22- (4-methoxy-phenyl) -ethyl-N- (2-piperidin-1-yl-phenyl) -hydrazine (f) The product (160 mg) is obtained according to the method of Step 4 of Example 1, using 250 mg of the previous derivative as an initial product and 322 mg of sodium nitrite in 3 mL of acetic acid, leading to the nitrous intermediate which was reduced by 103 mg of lithium aluminum hydride (4 equivalents) in 3 mL of tetrahydrofuran with reflux. Yield: 61% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.80-7.38 (aromatic mass, 8H), 3.77 (s, 3H), 3.42 (t, 2H), 3.08 (t, 2H), 2.93 ( m, 4H), 1.55-1.70 (m, 6H) HPLC: 88% MS: MH + 326.

Step 3: Methyl 5-Bromo-2-methoxy-4- (N-r2- (4-methoxyphenyl) -ethyl-N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl) -benzoate To a solution of 160 mg of the previous compound in 3 mL of dimethylformamide, was added 164 mg of the acid of preparation 2 (1.1 equivalents), 104 mg of EDCI (1.1 equivalents) and 73 mg of HOBt (1.1 equivalents). The reaction medium was stirred at room temperature for 30 minutes and then heated at 40 ° C for 1 hour 30. The crude reaction product was poured onto ice and extracted with ethyl acetate several times. The organic phases were dried over magnesium sulfate, filtered and evaporated under reduced pressure. A first chromatography on silica gel of the residue (petroleum ether / ethyl acetate: 95/5, 80/20 and then 50/50) was able to isolate the product, which was then purified by reverse phase chromatography (conditions: column C18, 21.2 x 150 mm, half Socratic 30% acetonitrile / H2O + 0.05% TFA, flow rate: 15 mL / minute, wavelengths: 220 and 254 nm), leading to 90 mg of the desired product as a salt of TFA. Yield: 25% 1 H NMR (DMSO, 300 MHz) d (ppm): 12.15 (broad s, 1 H), 1 1.53 (s, 1 H), 8.06 (d, 1 H), 7.92 (s, 1 H) , (m, 1 H), 7.54 (t, 1 H), 7.42 (m, 1 H), 7.32 (d, 1 H), 7.03 (d, 3H), 6.76 (d, 2H), 3.86 and 3.83 ( 2s, 10H), 3.73 (s, 2H), 3.47 (s, 3H), 2.98 (m, 2H), 2.85 (t, 2H), 1.79 (m, 4H), 1.34 (m, 2H). HPLC: 99% MS: MH + 610/612.

Step 4: 5-Bromo-2-methoxy-4- hydrochloride. { N- [2- (4-methoxy-phenyl) -etin-N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl) benzoic acid (6) The product (63 mg) is obtained as a hydrochloride in accordance with method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 68% P. f .: 162-176 ° C Elemental analysis calculated for: C3oH34BrN3O5.1 HCI.1.5H2O: C, 54.59; H, 5.80; N, 6.37. Found: C, 54.65; H, 5.31; N, 5.85. HPLC: 90% MS: MH + 596/598.

EXAMPLE 7 5-Bromo-2-methoxy-4-rN- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-phenyl) -hydrazinocarbonylmethylene-benzoic acid hydrochloride (7) ) Step 1: (4-methoxy-phenyl) - (2-methyl-6-nitro-phenyl) -amine The product (487 mg) is obtained according to the method of step 1 of Example 4, using 1 g of 2 -fluoro-3-methyl-nitrobenzene and 1.19 g of 4-methoxyaniline in the presence of 1.16 g of potassium tert-butanolate in 9 mL of DMSO. Yield: 29% H NMR (CDCl 3, 300 MHz) d (ppm): 7.99 (d, 1 H), 7.37 (m, 1 H), 6.96 (t, 1 H), 6.78 (m, 4 H), 3.78 ( s, 3H), 1.99 (s, 3H).

Step 2: N-2- (4-methoxy-phenyl) -3-methyl-benzene-1,2-diamine The product (428 mg) is obtained according to the method of step 2 of Example 1, using 487 mg of the previous derivative as an initial product and 2.13 g of tin chloride hydrate in 6 ml_ of ethanol. Yield: 99% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.99 (t, 1 H), 6.75 (m, 2 H), 6.65 (d, 2 H), 6.52 (m, 2 H), 3.74 (s, 3H), 2.17 (s, 3H).

Step 3: (4-methoxy phenyl) - (2-methyl-6-piperidin-1-l-phenyl) -amine The product (250 mg) is obtained according to the method of step 3 of Example 4, using 425 mg of the previous derivative as a starting product, 253 μg of dibromopentane and 778 pL of DIPEA in 8 ml of toluene. Yield: 45% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.95 (m, 3 H), 6.78 (m, 2 H), 6.67 (m, 2 H), 3.77 (s, 3 H), 2.73 (m, 4 H) ), 2.10 (s, 3H), 1 .59 (m, 6H).

Step 4: N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidinyl-yl-phenyl) -hydrazine (g) According to the method of step 4 of Example 1, the nitroso intermediate ( 270 mg) is obtained by extraction with dichloromethane from the buffering reaction medium at pH 7, using 250 mg of the previous derivative as a starting product and 337 mg of sodium nitrite in 3 mL of acetic acid. A suspension of 126 mg of lithium aluminum hydride (4 equivalents) in 3 mL of tetrahydrofuran applied to this intermediate for 1 hour with reflux, can lead to 129 mg of hydrazine after purification. Yield: 49% MS: MH + 312.

Step 5: Methyl 5-bromo-2-methoxy-4- [N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazino-carbonylmethylbenzoate ( 7a) To a solution of 129 mg of the acid obtained in Preparation 2 (1.1 equivalents) in 4 mL of dichloromethane, was added 100 pL of thionyl chloride (3.3 equivalents) and 1 drop of dimethylformamide. Everything was stirred for 1 hour at room temperature and then evaporated under reduced pressure. The acid chloride thus obtained, taken in 4 mL of toluene, was successively added a solution of 129 mg of the previous hydrazine in 3 mL of toluene and 65 pL of triethylamine (1.1 equivalents). The medium was heated overnight at 40 ° C and then after returning to room temperature, hydrolyzed and extracted with ethyl acetate several times. The collected organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The obtained residue was purified by reverse phase chromatography (conditions: C18 column, 21.2 x 150 mm, 35% acetic acid / H20 + SO5 medium, 0.05% TFA, flow rate: 15 mL / minute, wavelengths : 220 and 254 nm), leading to 10 mg of the expected product as a TFA salt. Yield: 37% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 12.52 (broad s, 1 H), 1 1.12. (s, 1 H), 7.98 (s, 1 H), 7.51 (m, 2H), 7.36 (d, 1 H), 7.13 (s, 1 H), 6.79 (d, 2H), 6.56 (d, 2H) ), 4.03 (m, 2H), 3.89 (s, 6H), 3.75 (s, 3H), 3.42 (m, 3H), 3.06 (m, 1 H), 2.26 (s, 3H), 1.79-2.01 (m, 5H), 1.50 (m, 1 H) HPLC: 93% MS: MH + 596/598.

Step 6: 5-Bromo-2-methoxy-4- [N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenol) -hydrazinocarbonylmethylbenzoic acid hydrochloride (7) ) The product (61 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 53% P. f .: 155-168 ° C Elemental analysis calculated for C29H32BrN305.1 HCI.1.75H2O: C, 53.55; H, 5.66; N, 6.46. Found: C, 53.28; H, 5.69; N, 6.12. HPLC: 100% MS: MH + 582/584.

EXAMPLE 8 5-Bromo-2-methox-fN- (4-methoxy-benzyl) -N- (2-piperidin-1-yl-phenyD-hydrazinocarbonylmethyl-benzoic acid hydrochloride (8) Step 1: (4-methoxy-benzyl) - (2-piperidin-1-yl-phenyl) -amine The product (644 mg) is obtained according to the method of step 1 of Example 3, using 1 g of 2-piperidinoaniline, 982 pl_ of 4-methoxybenzyl bromide (1.2 equivalents) and 1.6 g of potassium carbonate (2 equivalents) in 0 mL of DMF. Yield: 40% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.42 (d, 2H), 7.1 1 (m, 2H), 7.01 (d, 2H), 6.81 (td, 1 H), 6.75 (dd) , 1 H), 4.41 (s, 2H), 3.88 (s, 3H), 2.99 (broad s, 4H), 1.82 (m, 6H) HPLC: 100% MS: MH + 297.

Step 2: N- (4-Methoxy-benzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine (h) The product (275 mg) is obtained according to the method of step 4 of Example 1, using 290 mg of the previous derivative as an initial product and 392 mg of sodium nitrite in 3 mL of acetic acid, leading to the nitroso intermediate, which is reduced by 140 mg of lithium aluminum hydride (4 equivalents) in 4 mL of tetra h id break not with reflux. Yield: 90% H NMR (CDCl 3, 300 MHz) d (ppm): 7.23 (m, 2H), 7.10 (m, 1 H), 7.00 (m, 3H), 6.87 (m, 2H), 4.47 (s, 2H), 3.82 (s, 3H), 3.10 (m, 4H), 1.59-1.77 (m, 6H) HPLC: 96% MS: MH + 312.

Step 3: Methyl 5-bromo-2-methoxy-4- (N- (4-methoxy-benzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-benzoate The product is obtained according to the method of step 5 of Example 7, using 161 mg of the acid of preparation 2 and 16 pL of thionyl chloride in the presence of a drop of dimethylformamide to form the acid chloride and 150 mg of the previous hydrazine in the presence of pl_ of triethylamine for coupling With a purification by reverse phase chromatography (conditions: C18 column, 21.2 x 150 mm, 35% acetonitrile / H2O medium + 0.05% TFA, flow rate: 15 mL / minute, wavelengths: 220 and 254 nm), 80 mg of the expected product could be isolated as a TFA salt Yield: 23% 1 H NMR (CDCl 3, 300 MHz) d (ppm) 11.90 (broad s), 10.57 (s, 1 H), 8.13 (d, 1 H), 7.87 (s, 1 H), 7.63 (t, 1 H), 7.48 (t, 1 H), 7.34 (d, 1 H), 7.12 (d, 2 H) , 6.76 (m, 3H), 4.47 (m, 2H), 3.89 (m, 1 H), 3.78, 3.86 and 3.89 (3s, 9H), 3 64 (s, 2H), 2.95-3.15 (m, 3H), 1.93 and 2.09 (2m, 5H), 1.49 (m, 1 H) HPLC: 93% MS: MH + 596/598.

Step 4: 5-Bromo-2-methoxy-4- [N- (4-methoxy-benzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-1-benzoic acid hydrochloride (8) The product (36 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 43% P. f .: 140-171 ° C Elemental analysis calculated for C29H32BrN3O5.1 HCI.1.75H2O: C, 53.55; H, 5.66; N, 6. 46. Found: C, 53.52; H, 5.58; N, 5.97. HPLC: 98% S.H + 582/584.

EXAMPLE 9 5-Bromo-4-rN- (4-cyclohexyl-phenyl) -N- (2-piperidin-1-yl-fenii) -hydrazinocarbonylmethin-2-methoxy-benzoic acid hydrochloride (9) Step 1: (4-cyclohexyl-phenyl) - (2-nitro-phenyl) -amine The product (280 mg) is obtained according to the method of step 1 of Example 4, using 400 pL of 2-fluoro-nitrobenzene and 1 g of 4-cyclohexylaniline in the presence of 683 mg of potassium tert-butanolate in 4 mL of DMSO. Yield: 25% H NMR (CDC, 300 MHz) d (ppm): 9.47 (broad s, 1 H), 8.19 (d, 1 H), 7.71 (d, 1 H), 7.45 (t, 1 H), 7.34 (t, 1 H), 7.10-7.24 (m, 3H), 6.71 (t, 1 H), 2.53 (m, 1 H), 1.35-1.95 (2m, 10H) HPLC: 87% MS: Mhf 297 Step 2: N- (4-cyclohexylphenyl) -benzene-1,2-diamine The product (154 mg) is obtained according to the method of step 2 of Example 1, using 280 mg of the previous derivative as a starting product and 1.07 g of tin chloride hydrate in 4 mL of ethanol. Yield: 61% H NMR (CDCl 3, 300 MHz) d (ppm): 6.95-7.12 (m, 4H), 6.68-6.82 (m, 4H), 2.40 (m, 1 H), 1.40 and 1.80 (2m, 10H HPLC: 91% MS: MH + 267.

Step 3: (4-cyclohexyl-phenyl) - (2-piperidin-1-yl-phenyl) -amine The product (395 mg) is obtained according to the method of step 3 of Example 4, using 700 mg of the derivative preceded as a starting product, 357 pL of dibromopentane and 1.1 mL of DIPEA in 10 mL of toluene. Yield: 45% 1 H NMR (CDC, 300 MHz) d (ppm): 7.30 (m, 1 H), 7.05-7.16 (m, 5H), 6.97 (t, 1 H), 6.80 (t, 1 H), 6.64 (broad s, 1 H), 2.82 (m, 4H), 2.45 (m, 1 H), 1.35-1.90 (m, 16H).

Step 4: N- (4-Cyclohexyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine The product (80 mg) is obtained according to the method of step 4 of Example 1, using 200 mg of the preceding derivative as a starting product and 240 mg of sodium nitrite in 3 mL of acetic acid, leading to the intermediate nitrous, which is reduced by 181 mg of lithium aluminum hydride (8 equivalents) in 3 mL of tetrahydrofuran with reflux. Yield: 38% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.75-7.25 (aromatic mass, 8H), 4.75 (broad), 2.97 (m, 4H), 2.42 (m, 1 H), 1.25- 1.90 (aliphatic mass, 16H) MS: MH + 350.

Step 5: Methyl 5-bromo-4-fN- (4-cyclohexylphenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazino-carbonylmethyl-2-methoxybenzoate The product is obtained in accordance with method of step 3 in Example 6, using 70 mg of the pre-hydrazine and 67 mg of the acid of preparation 2, in the presence of 42 mg of EDCI and 30 mg of HOBt in 3 mL of dimethylformamide. With a purification by reverse phase chromatography (conditions: C18 column, 21.2 x 150 mm, 50% acetic acid 50% acetonitrile / H20 + 0.050% TFA, flow rate: 15 mL / minute, wavelengths: 220 and 254 nm), 32 mg of the expected product could be isolated as a TFA salt. Yield: 21% HPLC: 93% MS: MH + 634/636.

Step 6: 5-Bromo-4-fN- (4-cyclohexyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-2-methoxybenzoic acid hydrochloride (9) The product (22 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained from the previous step. Yield: 68% P.f .: 163-181 ° C Elemental analysis calculated for C33H38HrN3O4.1 HCI.0.75H2O: C, 59.; H, 6.09; N, 6. 27. Found: C, 59.23; H, 6.25; N, 6.03. HPLC: 93% MS: MH + 620/622.

EXAMPLE 10 5-Bromo-2-methoxy-4- [N- (2-methyl-6-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxy-phenyl) -hydrazinocarbonylmethyl-benzoic acid hydrochloride ( 10) Step 1: (2-methyl-6-nitro-phenyl) - (4-trifluoromethoxyphenyl) -amine The product (1.92 g) is obtained as a hydrochloride according to the method of step 1 of Example 4, using 1 g of 2-fluoro-3-methyl-nitrobenzene and 1.3 mL of 4-trifluoromethoxy-aniline in the presence of 1.16 g of potassium tert-butanolate in 10 mL of DMSO. Yield: 95% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 8.19 (broad s), 7.97 (d, 1 H), 7.45 (d, 1 H), 7.10 (m, 3 H), 6.74 (d, 2H), 2.1 1 (s, 3H) HPLC: 75% MS: MH + 313.

Step 2: 3-Methyl-N-2- (4-trifluoromethoxy-phenyl) -benzene-1,2-diamine The product (901 mg) is obtained according to the method of step 2 of Example 1, using 1.92 g. of the preceding derivative as a starting product and 6.94 g of tin chloride hydrate in 25 mL of ethanol. Yield: 52% 1 H NMR (CDC, 300 MHz) d (ppm): 7.07 (m, 3H), 6.73 (m, 2H), 6.53 (d, 2H), 5.10 (broad s, 1 H), 3.99 (s) broad, 2H), 2.18 (s, 3H) HPLC: 90% MS: MH + 283.

Step 3: (2-methyl-6-piperidin-1-yl-phenyl) - (4-trifluoromethoxy-phenyl) -amine The product (890 mg) is obtained according to the method of step 3 in Example 4, using 900 mg of the preceding derivative as a starting product, 433 μg of dibromopentane and 1.3 ml of DIPEA in 15 ml of toluene. Yield: 79% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.04 (m, 3H), 6.95 (d, 2H), 6. 66 (d, 2H), 6.19 (broad s, 1 H), 2.72 (m, 4H), 2.1 1 (s, 3H), 1.56 (m, 6H) HPLC: 96% MS: Mhf 351.

Step 4: N- (2-methyl-6-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxy-phenyD-hydrazine (i) The product (270 mg) contaminated by the starting amine is obtained from according to step 4 of Example 1, using 450 mg of the preceding derivative as a starting product and 514 mg of sodium nitrite in 4 mL of acetic acid, leading to the nitroso intermediate, which is reduced by 355 mg of lithium hydride and aluminum (8 equivalents) in 4 mL of tetrahydrofuran with reflux Estimated yield: 23% MS: MH + 366.

Stage 5: Methyl 5-bromo-2-methoxy-4- [N- (2-methyl-6-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxy-phenyl) -hydrazinocarbonylmethylbenzoate The product is obtained according to the method of step 3 of Example 6, using 400 mg of the above hydrazine and 365 mg of the acid of preparation 2 in the presence of 231 mg of EDCI and 163 mg of HOBt in 4 ml of dimethylformamide. With purification by reverse phase chromatography (conditions: column C18, 21.2 x 150 mm, half-Socratic 35% acetonitrile / H2O + 0.05% TFA, flow rate: 15mL / minute, wavelengths 220 and 254 nm), it was possible to isolate 260 mg of the expected product as a TFA salt. Yield: 36% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 12.26 (broad s, 1 H), 1 1 .42 (s, 1 H), 7.94 (s, 1 H), 7.50 (m, 3H ), 7.09 (m, 3H), 6.62 (d, 2H), 4.02 (m, 2H), 3.87 (s, 6H), 3.60 (m, 1 H), 3.31 (m, 2H), 3.15 (m, 1) H), 2.24 (s, 3H), 2.14 (m, 1 H), 1.79 1.94 (m, 4H), 1.52 (m, 1 H) HPLC: 95% MS: Mhf 650/652.

Step 6: 5-Bromo-2-methoxy-4-fN- (2-methyl-6-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxy-phenyl) -hydrazinecarbonylmethyl acid hydrochloride] The product ( 166 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 62% P.f .: 128 ° C (decomposition) Elemental analysis calculated for C29H29BrF3N3O5. I HCI. I H2O: C, 50.41; H, 4.67; N, 6.08. Found: C, 50.02; H, 4.68; N, 5.82. HPLC: 96% MS: MH + 636/638.

EXAMPLE 11 5-Bromo-2-methoxy-4- [N- (4'-methoxybiphenyl-4-yl) -N- (2-piperidin-1-yl-phenyD-hydrazinocarbonylmethyl-benzoic acid hydrochloride (11) Step 1: (4-bromo-phenyl) - (2-nitro-phenyl) -amine The product (6.49 g) is obtained according to the method of step 1 of Example 4, using 3.73 mL of 2-fluoro-nitrobenzene and 7.31 g of 4-bromoaniline in the presence of 6.36 g of potassium tert-butanolate in 120 mL of DMSO. Yield: 62% 1 H NMR (CDC, 300 MHz) d (ppm): 9.38 (broad s, 1 H), 8.19 (d, 1 H), 7.51 (d, 2 H), 7.38 (t, 1 H), 7.17 (t, 3H), 6.81 (t, 1 H) HPLC: 99% MS: MH + 293/295.

Step 2: N- (4-Bromophenyl) -benzene-1,2-diamine The product (571 mg) is obtained according to the method of step 2 of Example 1, using 723 mg of the previous derivative as an initial product and 2.78 g of tin chloride hydrate in 7 mL of ethanol. Yield: 88% 1 H NMR (CDC, 300 MHz) d (ppm): 7.26 (d, 2H), 7.05 (m, 2H), 6.78 (m, 2H), 6.60 (d, 1 H) HPLC: 97% MS : MH + 263/265.

Step 3: (4-bromo-phenyl) - (2-piperidin-1-yl-phenyl) -amine The product (1.03 g) is obtained according to the method of step 3 of Example 4, using 1.35 g of the previous derivative as a starting product, 698 pL of dibromopentane and 2.1 mL of DIPEA in 13 mL of toluene. Yield: 61% 1 H NMR (COCl 3, 300 MHz) d (ppm): 7.36 (m, 2 H), 7.26 (m, 1 H), 7.01-7.10 (m, 4 H), 6.89 (m, 1 H), 6.56 (s broad, 1 H), 2.82 (t, 4H), 1.57-1.74 (m, 6H) HPLC: 100% MS: MH + 331/33.

Step 4: (4'-methoxy-biphenyl-4-yl) - (2-piperidin-1-yl-phenyl) -amine To a solution of 554 mg of the brominated derivative previously obtained in 14 ml_ of a 50:50 mixture of methanol / toluene, 380 mg of phenylboronic acid (1.5 equivalents), 96 mg of tetracis palladium (0.05 equivalents), 212 mg of lithium chloride (3 equivalents) and 4.17 ml_ of a 1 molar solution of sodium carbonate were added sequentially. calcium. All was refluxed for 2 hours. The crude reaction product was extracted with ethyl acetate several times; The collected organic phases were washed with water, and then dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue obtained was purified by chromatography on silica gel (petroleum ether and then petroleum ether / ethyl acetate: 99/1), yielding 260 mg of the expected product. Yield: 43% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.53 (m, 4 H), 7.38 (dd, 1 H), 7.25 (m, 2 H), 7.12 (dd, 1 H), 6.97-7.10 (m, 3H), 6.88 (td, 1 H), 6.76 (broad s, 1 H), 3.86 (s, 3H), 2.87 (t, 4H), 1.52-1.78 (m, 6H) HPLC: 80 % MS: MH + 359.

Step 5. N- (4'-methoxy-biphenyl-4-yl) -N- (2-pipericlin-1-yl-phenyl) -hydrazine (k) The product (141 mg) is obtained according to the method of step 4 of Example 1, using 203 mg of the previous derivative as an initial product and 226 mg of sodium nitrite in 1.5 mL of acetic acid, leading to the nitroso intermediate, which is reduced by 179 mg of lithium hydride and aluminum (8 equivalents) in 4 mL of tetra h id break not with reflux. Yield: 64% H NMR (CDCl 3, 300 MHz) d (ppm): 7.49 (d, 2H), 7.38 (d, 2H), 7. 14 (m, 2H), 6.93 (m, 4H), 6.87 (d, 2H), 3.84 (s, 3H), 2.92 (m, 4H), 1.39 (m, 6H) HPLC: 90% MS. MH + 374.

Step 6: Methyl 5-bromo-2-methoxy-4- [N- (4'-methoxybiphenyl-4-yl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethylbenzoate The product is obtained according to the method of step 3 of Example 6, using 141 mg of the pre-hydrazine and 126 mg of the acid of preparation 2 in the presence of 79 mg of EDCI and 56 mg of HOBt in 6 mL of dimethylformamide. With a purification by reverse phase chromatography (conditions: column C18, 21.2 x 150 mm, half Socratic 50% acetonitrile / h O + 0.05% TFA, flow rate: 15 mL / minute, wavelengths: 220 and 254 nm), 9 mg of the expected product could be isolated as a salt of TFA. Performance (not optimized): 3% HPLC: 75% MS: MH + 658/660.

Step 7: 5-Bromo-2-methoxy-4- (N- (4'-methoxy-biphenyl-4-yl) -N- (2-piperidin-1-yl-phenyl) -hydrazine-carbonylmethyl-hydrochloride benzoic (11) The product (7.3 mg) is obtained as a hydrochloride according to the method of step 6 or example 2, using the product obtained in the previous step as a substrate Yield: 92% HPLC: 80% MS: MH + 644/646.

EXAMPLE 12 5-Bromo-4-fN- (4-cyclohexyloxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine-carbonylmethane-2-methoxy-benzoic acid hydrochloride (12) Step 1: 1-cyclohexyloxy-4-nitro-benzene To 3.9 g of cyclohexanol (1.1 equivalents) placed in the presence of 2.12 g of sodium hydride (1.5 equivalents) under stirring for 10 minutes, a solution of 5 g was added of 4-fluoronitrobenzene in 75 ml_ of dimethylformamide. Everything was heated at 60 ° C for 5 hours. After returning to room temperature, the medium was hydrolyzed and the crude reaction product was extracted with ethyl acetate several times. The organic phases were dried over magnesium sulfate, filtered and evaporated under reduced pressure. With chromatography on silica gel of the residue (cyclohexane and then cyclohexane / ethyl acetate: 98/2 and 90/10), the isolation of 6.06 g of the desired product was possible. Yield: 78% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 8.16 (d, 2 H), 6.92 (d, 2 H), 4.37 (m, 1 H), 1.98 (m, 2 H), 1.81 ( m, 2H), 1.35-1.65 (m, 6H) HPLC: 98% MS: [M + Na] + 244.

Step 2: 4-cyclohexyloxy-phenylamine The product (4.48 g) is obtained according to the method of step 2 of Example 5, using 6.06 g of the previous derivative as a starting product and 30.9 g of tin chloride hydrate in 59 mL of ethanol. Yield: 87% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.76 (d, 2 H), 6.62 (d, 2 H), 4.06 (m, 1 H), 3.42 (broad s, 2 H), 1.95 (m , 2H), 1.78 (m, 2H), 1.28-1.60 (m, 6H) HPLC: 88% MS: MH + 192.

Step 3: (4-cyclohexyloxy phenyl) - (2-nitro-phenyl) -amine The product (4.27 g) is obtained according to the method of step 1 of Example 4, using 2.95 mL of 2-fluoro-nitrobenzene and 4.48 g of the product obtained in the previous step in the presence of 4.18 g of potassium tert-butanolate in 108 mL of DMSO. Yield: 59% H NMR (CDCl 3, 300 MHz) d (ppm): 9.40 (broad s, 1 H), 8.20 (d, 1 H), 7.35 (m, 1 H), 7.18 (m, 2H), 6.95 -7.05 (m, 3H), 6.72 (m, 1 H), 4.06 (m, 1 H), 2.05 (m, 2H), 1.82 (m, 2H), 1.35-1.60 (m, 6H) HPLC: 86% MS: MH + 313.

Step 4: N- (4-cyclohexyloxy-phenyl) -benzene-1,2-diamine The product (3.43 g) is obtained according to the method of step 2 of Example 1, using 4.27 g of the previous derivative as a product of start and 15.42 g of tin chloride hydrate in 27 mL of ethanol. Yield: 88% H NMR (CDCl 3, 300 MHz) d (ppm): 7.04 (d, 1 H), 6.94 (m, 1 H), 6.72-6.84 (m, 6H), 4.14 (m, 1 H), 1.97 (m, 2H), 1.80 (m, 2H), 1.30-1.60 (m, 6H). HPLC: 92% MS: MH + 283.

Step 5: (4-cyclohexyloxy-phenyl) - (2-piperidin-1-yl-phenyl) -amine The product (1.55 g) is obtained according to the method of step 3 of Example 4, using 3.43 g of the derivative previous as a starting product, 1.65 ml_ of dibromopentane and 5.1 ml_ of DIPEA in 49 ml of toluene. Yield: 36% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.07 (m, 4H), 6.80-6.98 (m, 3H), 6.78 (m, 1 H), 6.52 (broad s, 1 H), 4.21 (m, 1 H), 2.86 (m, 4H), 1.35-2.05 (m, 16H) HPLC: 99% MS: MH + 351.

Step 6: N- (4-cyclohexyloxyphenyl) -N- (2-piperidin-1-phenyl) -hydrazine The product (18 mg) is obtained according to the method of step 4 of Example 1, using 500 mg of the previous derivative as an initial product and 571 mg of sodium nitrite in 4 ml_ of acetic acid, leading to the intermediate nitrous, which is reduced by 431 mg of lithium aluminum hydride (8 equivalents) in 4 ml_ of tetra h id break not with reflux. Yield: 23% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.00-7.18 (m, 5H), 6.94 (m, 1 H), 6.90 (m, 2H), 4.77 (broad s, 1 H), 4.09 (m, 1 H), 2.98 (m, 4H), 2.00 (m, 2H), 1.80 (m, 2H), 1.24-1.67 (m, 12H) HPLC: 94% MS: MH + 366.

Stage 7: Methyl 5-bromo-4- [N- (4-cyclohexyloxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethane-2-methoxybenzoate The product is obtained according to the method of step 3 of Example 6, using 50 mg of the previous hydrazine and 46 mg of the acid of preparation 2 in the presence of 29 mg of EDCI and 20 mg of HOBt in 1.5 ml of dimethylformamide . With a purification by reverse phase chromatography of a fraction (conditions: column C18, 21.2 x 150 mm, half-Socratic 45% acetonite / H20 + 0.05% TFA, flow rate: 15 mL / minute, wavelengths : 220 and 254 nm) 57 mg of the expected product could be isolated as a TFA salt. Estimated yield: 54% HPLC: 92% MS: MH + 650/652.

Step 8: 5-Bromo-4-fN- (4-cyclohexyloxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-2-methoxybenzoic acid hydrochloride (12) The product (61 mg) it is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 85% P.f .: 145-180 ° C HPLC: 91% MS: MH + 636/638.

EXAMPLE 13 5-Bromo-2-methoxy-4- [N- (4-phenoxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonyl-methyl] -benzoic acid hydrochloride (13) Step 1: (2-nitrophenyl) - (4-phenoxy-phenyl) -amine The product (2.03 g) is obtained according to the method of step 1 of Example 4, using 3.7 mL of 2-fluoro-nitrobenzene and 7.88 g of 4-phenoxyaniline in the presence of 6.36 g of potassium tert-butanolate in 34 mL of DMSO. Yield: 18% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 9.44 (broad s, 1 H), 8.20 (d, 1 H), 7.37 (m, 3 H), 7.25 (m, 2 H), 7.05- 7.18 (m, 6H), 6.76 (m, 1 H) HPLC: 80% MS: MH + 307.

Step 2: N- (4-phenoxy-phenyl) -benzene-1,2-diamine The product (709 mg) is obtained by catalytic hydrogenation in the presence of 203 mg of 10% palladium on carbon in 40 mL of ethanol.

Yield: 38% 1 H NMR (CDC, 300 MHz) d (ppm): 7.30 (m, 2H), 6.90-7.12 (m, 7H), 6.70-6.85 (m, 4H) HPLC: 100% MS: MH + 277.

Step 3: (4-phenoxyphenyl) - (2-piperidin-1-yl-phenyl) -amine The product (799 mg) is obtained according to the method of step 3 of Example 4, using 709 mg of the previous derivative as a starting product, 350 pL of dibromopentane and 1.07 mL of DIPEA in 10 mL of toluene. Yield: 82% 1 H NMR (DMSO, 300 MHz) d (ppm): 7.40 (d, 1 H), 7.25 (m, 4H), 7.03 (m, 4H), 6.95 (m, 4H), 3.37 (m, 4H), 1.90 (m, 4H), 1.61 (m, 2H) HPLC: 100% MS: MH + 345.

Step 4: N- (4-phenoxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine (m) The product (185 mg) is obtained according to the method of step 4 of Example 1 , using 400 mg of the previous derivative as an initial product and 420 mg of sodium nitrite in 3 mL of acetic acid, leading to the nitrous intermediate, which is reduced by 319 mg of lithium aluminum hydride (8 equivalents) in 3 mL of tetrahydrofuran with reflux. Yield: 49% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.92-7.26 (m, 13H), 4.82 (broad s, 2H), 2.97 (m, 4H), 1.55-1.69 (2m, 6H) HPLC : 97% MS: MH + 360.

Stage 5: Methyl 5-bromo-2-methoxy-4- (N- (4-phenoxyphenyl) -N- (2-piperidin-1-yl-phenyl-hydrazinocarbonylmethylbenzoate) The product (270 mg) is obtained in accordance with the method of step 3 of Example 6, using 185 mg of the previous hydrazine and 172 mg of the acid of preparation 2 in the presence of 108 mg of EDCI and 76 mg of HOBt in 3 mL of dimethylformamide. 1 H NMR (CDC, 300 MHz) d (ppm): 9.35 (broad s, 1 H), 7.97 (d, 1 H), 6.75-7.50 (aromatic mass, 14H), 3.70-3.94 (3s, 8H), 2.68 (m, 4H), 1.46-1.59 (m, 6H) HPLC: 77% MS: MH + 644/646.

Step 6: 5-Bromo-2-methoxy-4-fN- (4-phenoxyphenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-1-benzoic acid hydrochloride (13) The product is obtained in accordance with the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. With purification by reverse phase chromatography of a fraction (conditions: C18 column, 21.2 x 150 mm, isocratic medium 35% acetonitrile / H20 + 0.05% TFA, flow rate: 15 mL / minute, wavelengths: 220 and 254 nm) followed by treatment with a 1N hydrochloric acid solution, the expected product could be isolated as a hydrochloride (89 mg). Yield: 32% P. f .: 232-235 ° C Elemental analysis calculated for C33H32BrN3O5. I HCI. I H2O: C, 57.86; H, 5.15; N, 6.13. Found: C, 57.74; H, 5.01; N, 5.89. HPLC: 97% MS: MH + 630/632.

EXAMPLE 14 5-Bromo-4- hydrochloride. { N-f4- (4-chloro-phenoxy) -phenin-N- (2-piperidin-1-yl-phene) -hydrazinocarbonylmethyl) -2-methoxy-benzoic (14) Step 1: [4- (4-Chloro-phenoxy) -phenyl-1- (2-nitrophenyl) -amine The product (609 mg) is obtained according to the method of step 1 of Example 4, using 840 μ? _ Of 2-fluoro-nitrobenzene and 2.1 g of 4- (chlorophenoxy) -aniline in the presence of 1.43 g of potassium tert-butanolate in 20 mL of DMSO. Yield: 22% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 8.21 (d, 1 H), 7.24-7.40 (m, 5H), 6.97-7.14 (m, 5H), 6.77 (t, 1 H) HPLC: 97% MS: MH + 341/343.

Step 2: N- [4- (4-Chloro-phenoxy) -phenn-benzene-1,2-diamine The product (524 mg) is obtained according to the method of step 2 of Example 1, using 609 mg of the previous derivative as an initial product and 2 g of tin chloride hydrate in 10 mL of ethanol. Yield: 94% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.73-7.38 (aromatic mass, 12H) HPLC: 100% MS: MH + 31 1/313.

Step 3: [4- (4-Chloro-phenoxy) -phenn- (2-piperidin-1-yl-phenyl) -amine The product (596 mg) is obtained according to the method of step 3 of Example 4, using 684 mg of the previous derivative as a starting product, 300 μl of dibromopentane and 920 μl of DIPEA in 15 mL of toluene. Yield: 71% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.80-7.28 (aromatic mass, 12H), 6.66 (broad s, 1 H), 2.86 (m, 4H), 1.72 (m, 4H ), 1.61 (m, 2H) HPLC: 99% MS: MH + 379/381.

Step 4: N- [4- (4-Chloro-phenoxy) -phenyl-N- (2-piperidin-1-yl-phenyl) -hydrazine (n) The product (80 mg) is obtained according to the method of step 4 of Example 1, using 300 mg of the previous derivative as an initial product and 317 mg of sodium nitrite in 3 mL of acetic acid, leading to the nitroso intermediate, which is reduced by 120 mg of lithium aluminum hydride ( 4 equivalents) in 5 mL of tetrahydrofuran. Yield: 26% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.86-7.25 (aromatic mass, 12H), 2.98 (m, 4H), 1.70 (m, 4H), 1.56 (m, 2H) HPLC: 83 % MS: MH + 394/396.

Step 5: 5-bromo-4-. { Methyl N-f4- (4-chlorophenoxy) -phenill-N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonyl-methyl) -2-methoxy-benzoate The product (86 mg) is obtained in accordance with method of step 3 of Example 6, using 80 mg of the previous hydrazine and 68 mg of the acid of preparation 2 in the presence of 43 mg of EDCI and 30 mg of HOBt in 3 mL of dimethylformamide. Yield: 62% 1 H NMR (CDCl 3i 300 MHz) d (ppm): 9.35 (broad s, 1 H), 7.97 (d, 1 H), 6.75-7.52 (aromatic mass, 13H), 3.67-3.91 (3s, 8H ), 2.68 (m, 4H), 1.42-1.59 (m, 6H) HPLC: 94% MS: MH + 678/680.

Step 6: 5-Bromo-4- (N-f4- (4-chloro-phenoxy) -phenill-N- (2-piperidin-1-yl-phenyl) -hydrazine-carbonylmethyl) -2-methoxy- hydrochloride benzoic (14) The product (52 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 62% P.f .: 153.5-163.5 ° C HPLC: 95% MS: MH + 664/666.

EXAMPLE 15 4- Hydrochloride. { N-f4- (4-fluoro-phenoxy) -phenyl-1 N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonyl-methyl) -2-methoxy-benzoic acid (15) Step 1: f4- (4-fluorophenoxy) -phenyl-1- (2-methyl-6-nitro-phenyl) -amine The product (790 mg) is obtained according to the method of step 1 of Example 4, using 900 μ? _ Of 2-fluoro-3-methyl-nitrobenzene and 2.6 g of 4- (4-fluorophenoxy) -phenylamine obtained in step 2 of Example 5 in the presence of 2.36 g of potassium tert-butanolate in 80 ml_ of DMSO. Yield: 40% H NMR (CDCl 3, 300 MHz) d (ppm): 8.38 (broad s, 1 H), 1.98 (d, 1 H), 7.40 (d, 1 H), 6.87-7.06 (aromatic mass , 35 7H), 6.76 (d, 2H), 2.08 (s, 3H) HPLC: 84% MS: MH + 339.

Step 2: N2-f4- (4-fluoro-phenoxy) -phenyl] -3-methyl-benzene-, 2-diamine The product (1.58 g) is obtained by hydrogenation according to the method of step 2 of Example 13 Yield: 87% 1 H NMR (CDC, 300 MHz) d (ppm): 6.83-7.01 (aromatic mass, H), 6.67 (d, 2 H), 6.55 (d, 2 H), 4.92 (broad s, 1 H) , 3.89 (broad s, 2H), 2.18 (s, 3H) HPLC: 98% MS: MH + 309.

Step 3: [4- (4-fluorophenoxy) -phenyl- (2-methyl-6-piperidin-1-yl-phenyl) -amine The product (1.16 g) is obtained according to the method of step 3 of Example 4, using 1.58 g of the previous derivative as a starting product, 700 μ? Of dibromopentane and 2.14 mL of DIPEA in 30 mL of toluene. Yield: 60% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.84-7.01 (aromatic mass, 9H), 6.70 (d, 2H), 6.18 (broad s, 1 H), 2.74 (m, 4H), 2.13 (s, 3H), 1.58 (m, 6H) HPLC: 98% MS: MH + 377.

Step 4: N- [4- (4-Fluoro-phenoxy) -phenill-N- (2-methyl-6-piperidin-1-phenyl-hydrazine (o) The product (198 mg) is obtained in accordance with the method of step 4 of Example 1, using 525 mg of the previous derivative as a starting product and 558 mg of sodium nitrite in 4 mL of acetic acid, leading to the nitroso intermediate, which is reduced by 208 mg of hydride lithium and aluminum (4 equivalents) in 4 ml_ of tetrahydrofuran Yield: 36% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.83-7.18 (aromatic mass, HH), 4.87 (broad s, 2H), 2.68 and 2.94 (4H, 2m), 2.12 (s, 3H), 1.50-1.64 (m, 6H) HPLC: 76% MS: MH + 392.

Stage 5: 4- (N-f4- (4-fluoro-phenoxy) -phenyl-N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinecarbonylmethyl) -2-methoxy-benzoate methyl Product (141 mg) is obtained according to the method of step 3 of Example 6, using 95 mg of the previous hydrazine and 60 mg of the acid of preparation 1 in the presence of 51 mg of EDCI and 36 mg of HOBt in 1.5 ml_ of dimethylformamide. Yield: 97% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 9.76 (broad s, 1 H), 7.74 (d, 1 H), 6.50-7.22 (aromatic mass, 13H), 3.87 (s, 3H) , 3.70 (m, 5H), 2.72 (m, 2H), 2.44 (s, 3H), 2.30 (m, 2H), 1.30-1.42 (2m, 6H) HPLC: 97% MS: MH + 598.

Stage 6: 4- Hydrochloride. { N-f4- (4-fluorophenoxy) -phenyl-1-N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl) -2-methoxybenzoic acid (15) The product (131 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 90% P.f .: 155-168 ° C HPLC: 100% MS: MH + 584.

EXAMPLE 16 5-Bromo-4- hydrochloride. { N- [4- (4-Fluoro-phenoxy) -phenn-N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazino-carbonylmethyl > -2-methoxy-benzoic (16) Step 1: 5-bromo-4- (N- [4- (4-fluoro-phenoxy) -phenyl-N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazonocarbonylmethyl) -2- Methyl methoxybenzoate (16a) The product (154 mg) is obtained according to the method of step 3 of Example 6, using 95 mg of the hydrazine of step 4 of Example 15 and 81 mg of the acid of the preparation 2 in the presence of 51 mg of EDCI and 36 mg of HOBt in .5 ml_ of dimethylformamide. Yield: 94% H NMR (CDC, 300 MHz) d (ppm): 9.86 (broad s, 1 H), 7.98 (s, 1 H), 6.84-7.23 (aromatic mass, 10H), 6.57 (d, 2H) , 3.87 (s, 3H), 3.76 (s, 2H), 3.71 (s, 3H), 2.80 (m, 2H), 2.44 (s, 5H), 1.37-1.48 (2m, 6H) HPLC: 91% MS: MH + 676/678.

Stage 2: 5-bromo-4- hydrochloride. { N- [4- (4-Fluoro-phenoxy) -phenn-N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazylcarbonyl-methyl) -2-methoxyben 06.}. The product (16 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 73% P. f .: 155-168 ° C Elemental analysis calculated for C34H33BrFN3O5.I HCI I .5H2O: C, 56.25; H, 5.14; N, 5.79. Found: C, 56.31; H, 5.04; N, 5.61. HPLC: 98% MS: MH + 662/664.

EXAMPLE 17 4-rN- (4-Benzyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-1-bromo-2-methoxy-benzoic acid hydrochloride (17) Step 1: (4-benzyl-phenyl) - (2-nitro-phenyl) -amine The product (621 mg) is obtained according to the method of step 1 of Example 4, using 958 pl_ of 2-fluoro-nitrobenzene and 2 g of 4-benzylaniline in the presence of 1.63 potassium tert-butanolate in 30 mL of DMSO. Yield: 22% H NMR (CDCl 3, 300 MHz) d (ppm): 9.46 (broad s, 1 H), 8.19 (d, 1 H), 7.71 (d, 1 H), 7.44 (m, 1 H), 7.10-7.40 (aromatic mass, 9H), 6.74 (m, 1 H), 4.01 (s, 2H) HPLC: 78% MS: [M + Na] + 327.

Step 2: N- (4-benzylphenyl) -benzene-1,2-diamine The product (291 mg) is obtained by hydrogenation according to the method of step 2 of Example 13. Yield: 52% HPLC: 100% MS : MH + 275.

Step 3: (4-benzyl-phenyl) - (2-piperidin-1-yl-phenyl) -amine The product (213 mg) is obtained according to the method of step 3 of Example 4, using 291 mg of the derivative previous as a starting product, 144 pl_ of dibromopentane and 444 pL of DIPEA in 4 mL of toluene. Yield: 59% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.79-7.32 (aromatic mass, 13H), 6.63 (broad s, 1 H), 3.94 (s, 2H), 2.83 (m, 4H), 1.70 (m, 4H), 1.58 (m, 2H) HPLC: 96% MS: MH + 343.

Step 4: N- (4-benzyl-phen-N- (2-piperidin-1-yl-phenyl) -hydrazine (p) The product (60 mg) is obtained according to the method of step 4 of Example 1, using 213 mg of the previous derivative as an initial product and 249 mg of sodium nitrite in 3 mL of acetic acid, leading to the nitrous intermediate, which is reduced by 189 mg of lithium aluminum hydride (8 equivalents) in 3 mL of tetrahydrofuran Yield: 27% H NMR (CDCl 3, 300 MHz) d (ppm): 6.92-7.31 (aromatic mass, I3H), 4.75 (broad s, 1 H), 3.91 (s, 2H), 2.96 (m, 4H), 1.66 (m, 4H), 1.54 (m, 2H) HPLC: 100% MS: MH + 358.

Stage 5; 4- [N- (4-benzyl-phenyl) -N- (2-piperidin-1-yl-pheno-hydrazinocarbonylmethyl-5-bromo-2-methoxy-benzoate methyl) The product (64 mg) is obtained in accordance with method of step 3 of Example 6, using 60 mg of the previous hydrazine and 56 mg of the acid of preparation 2 in the presence of 35 mg of EDCI and 25 mg of HOBt in 1 ml_ of dimethylformamide Yield: 59% H NMR (CDCl 3, 300 MHz) d (ppm): 9.33 (broad s, 1 H), 7.98 (d, 1 H), 6.71-7.51 (aromatic mass, 14H), 3.95 (s, 6H), 3.70 and 3.76 (2s) , 4H), 2.74 (m, 4H), 1.28-1.60 (m, 6H) HPLC: 90% MS: MH + 642/644.

Stage 6: 4- Hydrochloride. { N- (4-benzyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -h -drazinocarbonylmethin-5-bromo-2-methoxybenzoic acid (17) The product (58 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 88% P. f .: 137.5-162 ° C HPLC: 97% MS: MH + 628/630.

EXAMPLE 18 4- [N- (4-Bromo-phenyl) -fN- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-S-chloro-2-methoxy-benzoic acid hydrochloride (18) Step 1: N- (4-bromo-phenyl) -N- (2-piperidin-1-ylphenyl) -hydrazine (q) The product (370 mg) is obtained according to the method of step 4 of Example 1, using 500 mg of the derivative obtained in step 3 of Example 11 as a starting product and 604 mg of sodium nitrite in 3 mL of acetic acid, leading to the nitroso intermediate, which is reduced by 458 mg of lithium aluminum hydride (8 equivalents) in 3 mL of tetrahydrofuran. Yield: 71% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.98-7.25 (aromatic mass, 8H), 4.77 (broad s, 2H), 2.92 (m, 4H), 1.66 (m, 4H), 1.55 (m, 2H) HPLC: 88% MS: MH + 346/348.

Step 2: 4- [N- (4-bromophenyl) -N- (2-piperidin-1-yl-phenylV -hydrazinocarbonylmethyl-5-chloro-2-methoxy-benzoate methyl Product (64 mg) is obtained in accordance with the method of step 3 of Example 6, using 370 mg of the pre-hydrazine and 304 mg of the acid of preparation 3 in the presence of 225 mg of EDCI and 159 mg of HOBt in 5 ml of dimethylformamide Yield: 89% H NMR (CDCl 3, 300 MHz) d (ppm): 9.34 (broad s, 1 H), 7.78 (d, 1 H), 6.63-7.49 (aromatic mass, 9H), 3.87 (2s, 6H), 3.70 (s, 2H), 2.75 (m, 4H), 1.28 and 1.60 (2m, 6H) HPLC: 96% MS: MH + 586/588.

Stage 3: 4- (N- (4-Bromo-phenyl) -N- (2-pyridin-1-yl-phenyl) -hydrazinocarbonylmethyl-5-chloro-2-methoxy-benzoic acid hydrochloride (8) The product (39 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step Yield: 75% P. f .: 177.2-189 ° C HPLC: 95% MS: MH + 572/574.

EXAMPLE 19 4-rN- (3'-Acetyl-biphenyl-4-yl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethin-5-chloro-2-methoxy-benzoic acid hydrochloride (19) Stage 1: methyl 4-rN- (3'-Acetyl-biphenyl-4-yl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-1-chloro-2-methoxy-benzoate To one solution of 200 mg of the brominated derivative obtained in step 2 of Example 18 in 2 mL of a 50:50 mixture of methanol / toluene were successively added 84 mg of 3-acetylphenylboronic acid (1.5 equivalents), 20 mg of tetracis palladium ( 0.05 equivalents) and 85 pL of a 1 molar solution of sodium carbonate. All was refluxed for 3 hours. The crude reaction product was taken up in water, extracted with ethyl acetate several times, the organic phases were collected, washed with a 1 molar solution of soda, and then dried over magnesium sulfate, filtered and evaporated under reduced pressure. The obtained residue was purified by chromatography on silica gel (petroleum ether / ethyl acetate: 90/10 and then 80/20 just up to 50/50), yielding 110 mg of the expected product. Yield: 51% H NMR (CDCl 3, 300 MHz) d (ppm): 9.35 (s, 1 H), 8.04 (d, 1 H), 7. 74 (m, 3H), 6.94-7.62 (aromatic mass, 8H), 6.80 (m, 2H), 2.79-3.62 (3s, 8H), 2.56 (m, 4H), 2.05 (s, 3H), 1.18-1.53 (m, 6H) HPLC: 92% MS: MH + 626/628.

Step 2: 4- [N-3'-Acetyl-biphenyl-4-yl) -N- (2-pyridin-1-yl-phenyl) -hydrazinocarbonylmethyl-5-chloro-2-methoxybenzoic acid hydrochloride The product (69 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 66% P. f .: 140.2-165.3 ° C HPLC: 91% MS: MH + 612/614.

EXAMPLE 20 4-rN- (4'-Acetyl-biphenyl-4-yl) -N- (2-piperidin-1-yl-phenyl) -h8-dicarinocarbonylmethyl-5-chloro-2-methoxy-benzoic acid hydrochloride ( twenty) Stage 1: 4- [N- (4'-Acetyl-biphenyl-4-yl) -N- (2-piperidin-1-yl-phenyl) -hydrazinecarbonylmethyl-1-methyl-2-chloro-2-methoxybenzoate The product (167 mg ) is obtained according to the method of step 1 of Example 19, using as a substrate the product obtained in step 2 of Example 18 and as a cosubstrate 4-acetylphenylboronic acid. Yield: 78% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 9.35 (s, 1 H), 6.70-7.91 (aromatic mass, 14H), 3.61-3.78 (3s, 8H), 2.60 (m, 4H) , 2.28 (s, 3H), 1.20-1.51 (m, 6H) HPLC: 87% MS: MH + 626/628.

Stage 2: 4- [N- (4'-Acetyl-biphenyl-4-in-N- (2-piperidin-1 -yl enyl) -hydrazinocarbonylmethyl-5-chloro-2-methoxybenzoic acid hydrochloride (20) The product (82 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step Yield: 47% P. f .: 165.3-190.1 ° C HPLC: 100% MS: MH + 612/614.

EXAMPLE 21 5-Bromo-2-methoxy-4- [N- (3-phenoxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-benzoic acid hydrochloride (21) Step 1: (2-nitro-phenyl) - (3-phenoxy-phenyl) -amine The product (2.08 g) is obtained according to the method of step 1 of Example 4, using 1.23 mL of 2-fluoronitrobenzene and 3.3 g of 3-phenoxyaniline in the presence of 2.13 g of potassium tert-butanolate in 10 mL of DMSO. Yield: 57% H NMR (CDCl 3, 300 MHz) d (ppm): 9.38 (broad s, 1 H), 8.12 (d, 1 H), 7.63 (d, 1 H), 6.70-7.43 (m, 11 H) HPLC: 79% MS: MH + 307.

Step 2: N- (3-phenoxy-phenyl) -benzene-1,2-diamine The product (1.88 g) is obtained by catalytic hydrogenation in the presence of 210 mg of 10% palladium on carbon in 40 mL of a mixture ethyl acetate / ethanol (1: 1). Yield: quantitative HPLC: 91% MS: MH + 277.

Step 3: (3-Phenoxy-phenyl) - (2-piperidin-1-phenyl) -amine The product (1.22 g) is obtained according to the method of step 3 of Example 4, using 1.88 g. of the previous derivative as a starting product, 925 pL of dibromopentane and 2.84 mL of DIPEA in 40 mL of toluene. Yield: 52% H NMR (CDC, 300 MHz) d (ppm): 6.83-7.19 (aromatic mass, 1 1 H), 6.72 (s, 1 H), 6.53 (dd, 1 H), 2.81 (m, 4H ), 1.50-1.74 (m, 6H) HPLC: 100% MS: MH + 345.

Step 4: N- (3-phenoxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine (r) The product (99 mg) is obtained according to the method of step 4 of Example 1, using 400 mg of the previous derivative as a starting product and 465 mg of sodium nitrite in 3 ml_ of acetic acid, leading to the nitroso intermediate, which is reduced by 159 mg of lithium aluminum hydride (4 equivalents) in 4 ml_ of tetrahydrofuran with reflux. Yield: 24% H NMR (CDCl 3, 300 MHz) d (ppm): 6.70-7.25 (aromatic mass, 12H), 6.28 (dd, 1 H), 4.68 (broad s, 2H), 2.85 (m, 4H), 1.46-1.63 (m, 6H) HPLC: 76% MS. MH + 360.

Step 5: Methyl 5-bromo-2-methoxy-4-f N- (3-phenoxyphenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-benzoate The product (168 mg) obtained according to the method of step 3 of Example 6, using 99 mg of the pre-hydrazine and 92 mg of the acid of preparation 2 in the presence of 58 mg of EDCI and 41 mg of HOBt in 1 ml of dimethylformamide. Yield: 95% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 9.35 and 9.40 (2 s broad, 1 H), 7.98 (2 s, 1 H), 6.41-7.40 (aromatic mass, 14 H), 3.70-3.95 (3s, 8H), 2.68 (m, 4H), 1.46-1.59 (m, 6H) HPLC: 96% MS: MH + 644/646.

Step 6: 5-Bromo-2-methoxy-4- [N- (3-phenoxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonyl-inethyl-1-benzoic acid hydrochloride (21) The product ( 124 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 71% P. f .: 142-159 ° C Elemental analysis calculated for C33H32BrN3O3.0.75HCI: C, 60.25; H, 5.02; N, 6.39. Found: C, 59.98; H, 5.11; N, 6.27. HPLC: 96% MS: MH + 630/632.

EXAMPLE 22 5-Bromo-2-methoxy-4- [N- (4-phenylsulfanyl-phenyl) -N- (2-pyridin-1-yl-phenyl) -hydrazinocarbonylmethane-benzoic acid hydrochloride 22) Step 1: 4-phenylsulfanyl-phenylamine To a solution of 5 g of 4-nitrophenyl sulfide in 100 mL of a mixture of ethanol / ethyl acetate (1: 1), 500 mg of 10% palladium on carbon was added. . Everything was placed under a hydrogen atmosphere (P = 10 bars) overnight. All was filtered over celite, rinsed and the filtrate was concentrated under reduced pressure leading to 3.57 g of the expected product. Yield: 82% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.10-7.35 (aromatic mass, 7H), 6.69 (d, 2H), 3.98 (broad s, 2H) HPLC: 86% MS: MH + 202.

Step 2: (2-nitrophenyl) - (4-phenylsulfanyl-phenyl) -amine The product (2.50 g) is obtained according to the method of step 1 of Example 4, using 1.25 mL of 2-fluoro-nitrobenzene and 3.57 g of the product obtained from the previous step in the presence of 2.12 g of potassium tert-butanolate in 10 mL of DMSO. Yield: 66% 1 H NMR (CDCb, 300 MHz) d (ppm): 9.48 (broad s, 1 H), 8.22 (d, 1 H), 7.11-7.42 (aromatic mass, 11H), 6.83 (m, 1H) HPLC: 96% MS: [M + Na] + 345.

Step 3: N- [4-phenylsulfanyl-phenyl-benzene-1,2-diamine The product (2 g) is obtained by catalytic hydrogenation using 2.50 g of the derivative previously obtained in the presence of 250 mg of 10% palladium on carbon in 30 mL of a mixture of ethanol / ethyl acetate (1: 1). Performance. 88% HPLC: 92% MS: MH + 293.

Step 4: (4-phenylsulfanyl-phenyl) - (2-piperidin-1-yl-phenyl) -amine The product (1.37 g) is obtained according to the method of step 3 of Example 4, using 2 g of the derivative previous as a starting product, 932 pL of dibromopentane and 2.86 mL of DIPEA in 40 mL of toluene. Yield: 55% 1 H NMR (CDCl 3, 300 MHz) d (ppm). 6.87-7.41 (aromatic mass, 13H), 6.78 (broad s, 1H), 2.84 (m, 4H), 1.74 (m, 4H), 1.60 (m, 2H) HPLC: 98% MS: MH + 361.

Step 5: N- (4-phenylsulfanyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine) The product (300 mg) is obtained according to the method of step 4 of Example 1 , using 800 mg of the previous derivative as a starting product and 888 mg of sodium nitrite in 5 ml_ of acetic acid, leading to the nitroso intermediate, which is reduced by 316 mg of lithium aluminum hydride (4 equivalents) in 5%. mL of tetrahydrofuran. Yield: 36% H NMR (CDCl 3, 300 MHz) d (ppm): 6.92-7.26 (aromatic mass, 13H), 4.71 (broad s, 2H), 2.84 (m, 4H), 1.58 (m, 4H), 1.47 (m, 2H) HPLC: 90% MS: MH + 376.

Step 6: Methyl 5-bromo-2-methoxy-4-fN- (4-phenylsulfanylphenyl) -N- (2-piperidin-1-phenyl-hydrazinocarbonylmethylbenzoate) The product (340 mg) is obtained according to the method of step 3 of Example 6, using 300 mg of the previous hydrazine as a substrate and 266 mg of the acid of preparation 2 as a co-substrate in the presence of 168 mg of EDCI and 118 mg of HOBt in 2.5 mL of dimethylformamide. 64% 1 H NMR (CDC, 300 MHz) d (ppm): 9.34 (broad s, 1 H), 7.99 (2 s, 1 H), 6.79-7.53 (aromatic mass, 14H), 3.70-3.92 (3s, 8H) , 2.71 (m, 4H), 1.48 and 1.60 (2m, 6H) HPLC: 91% MS: MH + 660/662.

Step 7: 5-Bromo-2-methoxy-4- [N- (4-phenylsul † anilphenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-1-benzohydrochloride (22) The product ( 108 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 83% P.f .: 158-166 ° C Elemental analysis calculated for C33H32BrN3O.tS.I HCI.I H2O: C, 56.54; H, 5.03 N, 5.99 Found: C, 56.59; H, 4.96; N, 5.84. HPLC: 95% MS: MH + 646/648.

EXAMPLES 23 AND 24 4-fN- (4-Benzenesulfonyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-1-bromo-2-methoxy-benzoic acid hydrochloride (23) and hydrochloride 4- [N- (4-benzenesulfinyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-bromo-2-methoxybenzoic acid (24) Stage 1: 4- [N- (4-benzenesulfonylphenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-5-bromo-2-methoxy-benzoate and 4- [N- (4- benzenesulfinylphenyl) -N- (2-pyridin-1-yl-phenyl) -hydrazinecarbonylmethyl-5-bromo-4-methoxy-benzoate methyl To a solution of 100 mg of the product obtained in step 6 of Example 22 in 3 mL of dichloromethane, an excess of methachloroperbenzoic acid (2 equivalents and 2 equivalents over time) was added until the total disappearance of the starting product (tracked by TLC). The crude reaction product was filtered, the filtrate was washed with a saturated solution of sodium sulfite and then sodium bicarbonate. The organic phases were dried over magnesium sulfate and then evaporated under reduced pressure to a mixture, which was purified by chromatography on silica gel (petroleum ether / ethyl acetate 60:40). 35 mg of each of the esters, the sulphonyl and sulfinyl forms, respectively, were obtained. Yield (sulfonyl): 33% HPLC: 83% MS: MH + 692/694 Yield (sulfinyl): 34% HPLC: 83% MS: MH + 676/778.

Step 2: 4- [N- (4-Benzenesulfonyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-5-bromo-2-methoxybenzoic acid hydrochloride (23) The product (20 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the sulfonyl derivative obtained in the previous step. Yield: 55% Elemental analysis calculated for C33H32BrN3O6S.0.75HCI: C, 56.15; H, 4.68; N, 5.95. Found: C, 56.09; H, 4.65; N, 5.67. HPLC: 84% MS: MH + 678/680.

Step 2: 4- [N- (4-Benzenesulfinyl-phenyl) -N- (2-pyridin-1-yl-phenyl) -hydrazinocarbonylmethyl-5-bromo-2-methoxy-benzoic acid hydrochloride The product (23 mg) is obtained as the hydrochloride according to the method of step 6 of Example 2, using as a substrate the sulfinil obtained in the previous step. Yield: 63% Elemental analysis calculated for C33H32BrN3O5S. I HCL .5H2O: C, 54.59; H, 5.00; N, 5.79. Found: C, 54.56; H, 4.91; N, 5.54. HPLC: 85% MS: MH + 662/664.

EXAMPLE 25 2-Methoxy-4-fE) -2-rN- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonyl] -hydrochloride vinyl > -benzoic acid (25) Step 1: 2-methoxy-4 - ((E) -2- [N- (4-methoxyphenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinecarbonyl-vinyl) - methyl benzoate The product (200 mg) is obtained according to the method of step 3 of Example 6, using 150 mg of the hydrazine of Example 7 as a substrate and 125 mg of the acid of preparation 4 as a co-substrate in the presence of 102 mg of EDCI and 72 mg of HOBt in 1.5 ml of dimethylformamide. Yield: 78% H NMR (CDCl 3, 300 MHz) d (ppm): 10.47 and 10.10 (broad 2s, 1 H), 7.95 (m, 2H), 7.20-7.48 (m, 6H), 6.65-7.10 (m, 4H), 4.1 1 (2s, 6H), 3.98 (s, 3H), 2.91 and 3.1 1 (m, 3H), 2.61 (m, 4H), 1.85 (m, 6H) HPLC: 98% MS: MH + 530.

Stage 2: 2-methoxy-4- hydrochloride. { (E) -2- [N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonyl) -benzoic acid. { 25) The product (149 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 71% Elemental analysis calculated for C30H33N3O5.I HCI.I.5H2O: C, 62.22; H, 6.44; N, 7.26. Found: C, 62.45; H, 6.34; N, 7.12. HPLC: 94% MS: MH + 516.

EXAMPLE 26 5-Bromo-2-methoxy-4- hydrochloride. { (E) -2-fN- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -h -drazinocarbonyl) -vinyl) -benzoic acid (26) Step 1: 5-bromo-2-methoxy-4-. { (E) -2- [N- (4-methoxyphenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonyl-1-vinyl) -benzoic acid methyl ester The product (234 mg) obtained according to the method of step 3 of Example 6, using 120 mg of hydrazine of Example 7 as a substrate and 134 mg of the acid of preparation 5 as a co-substrate in the presence of 81 mg of EDCI and 57 mg of HOBt in 2 mL of dimethylformamide. Yield: quantitative H NMR (CDC, 300 MHz) d (ppm): 10.37 and 9.95 (broad 2s, 1 H), 8.02 (m, 2H), 7.00-7.29 (m, 5H), 6.43-6.88 (m, 4H ), 3.95 (3s, 9H), 2.70 and 2.90 (m, 3H), 2.40 (m, 4H), 1.60 (m, 6H) HPLC: 87% MS: MH + 608/610.

Step 2: 5-Bromo-2-methoxy-4 - ((E) -2-fN- (4-methoxyphenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonyl-1-hydrochloride -vinyl) -benzoic acid (26) The product (217 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 86% P. f .. 192-206 ° C Elemental analysis calculated for C30H32BrN3O5. I HCI. I H2O: C, 55.52; H, 5.44; N, 6.47. Found: C, 55.43; H, 5.51; N, 6.37. HPLC: 91% MS: MH + 594/596.

EXAMPLE 27 4-fN- (4-Benzyl-phenyl) -fN- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazanocarbonylmethyl] -5-bromo-2-methoxy-benzoic acid hydrochloride ( 27) Step 1: (4-benzyl-phenyl) - (2-methyl-6-nitro-phenyl) -amine The product (1.01 g) is obtained according to the method of step 1 of Example 4, using 1.13 g of 2 -fluoro-3-methyl-nitrobenzene and 2 g of 4-benzylaniline in the presence of 1.31 g of potassium tert-butanolate in 30 mL of DMSO. Estimated yield: 35% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 8.32 (broad s, 1 H), 7.96 (d, 2 H), 6.68-7.51 (aromatic mass, 10 H), 3.93 (s, 2 H) ), 2.06 (s, 3H) HPLC: 79% MS: MH + 319.

Step 2: N2- (4-benzyl-phenyl) -3-methyl-benzene-1,2-diamine The product (530 mg) is obtained by hydrogenation according to the method of step 2 of Example 13. Yield: 58 % 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.99-7.32 (aromatic mass, 8H), 6.68 (d, 2H), 6.52 (d, 2H), 3.89 (s, 2H), 2.18 (s, 3H).

Step 3: (4-benzyl-phenyl) - (2-methyl-6-piperidin-1-yl-phenyl) -amine The product (460 mg) is obtained according to the method of step 3 of Example 4 , using 525 mg of the previous derivative as a starting product, 247 μ? _ of dibromopentane and 760 μ? _ of DIPEA in 10 mL of toluene. Yield: 71% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 6.92-7.31 (aromatic mass, 10H), 6.62 (d, 2H), 6.17 (broad s, 1H), 3.90 (s, 2H), 2.72 (m, 4H), 2.10 (s, 3H), 1.56 (m, 6H) HPLC: 98% MS: MH + 357.

Step 4: N- [4-benzyl-phenyl-N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine (t) The product (102 mg) is obtained according to the step method 4 of Example 1, using 450 mg of the previous derivative as an initial product and 505 mg of sodium nitrite in 3 mL of acetic acid, leading to the nitroso intermediate, which is reduced by 192 mg of lithium aluminum hydride (4 equivalents) ) in 5 mL of tetrahydrofuran. Estimated yield: 22% H NMR (CDCl 3, 300 MHz) d (ppm): 7.12-7.29 (aromatic mass, 6H), 6.97 (dd, 4H), 6.75 (d, 2H), 3.88 (s, 2H), 2.80 (m, 4H), 2.08 (s, 3H), 1.52 (m, 6H) HPLC: 64% MS: MH + 372.

Step 5: 4- [N- (4-benzyl-phenyl) -N- (2-methyl-6-piperidin-1-ylphenyl) -hydrazinocarbonylmethine-5-bromo-2-methoxy-benzoate methyl Product (91 mg ) is obtained according to the method of step 3 of Example 6, using 101 mg of the previous hydrazine and 91 mg of the acid of preparation 2 in the presence of 58 mg of EDCI and 41 mg of HOBt in 4 ml_ of dimethylformamide . Yield: 51% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 9.97 and 9.79 (broad s, 1 H), 7.97 (s, 1 H), 6.75-7.27 (aromatic mass, 11 H), 6.51 (d) , 2H), 3.87 (s, 6H), 3.72 (s, 4H), 2.74 (m, 2H), 2.37 (s, 3H), 2.36 (m, 2H), 1.40 (m, 6H) HPLC: 96% MS : MH + 656/658.

Step 6: 4-rN- (4-benzylphenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-5-bromo-2-methoxybenzoic acid hydrochloride (27) The product (74 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 84% P.f .: 173-187 ° C Elemental analysis calculated for C35H36BrN3O4.I HCI. I H2O: C, 60.31; H, 5.64; N, 6.03. Found: C, 60.36; H, 5.62; N, 5.99. HPLC: 98% MS: MH + 642/644.

EXAMPLE 28 5-Bromo-2-methoxy-4-fN- (4'-methoxy-biphenyl-4-yl) -N- (2-methyl-6-pyridin-1-yl-phenyl) -hydrochloride hydrocarbonylmethane-benzoic acid (28) Step 1: (4-bromo-phenyl) - (2-methyl-6-nitro-phenyl) -amine The product (2.44 g) is obtained according to the method of step 1 of Example 4, using 1.8 g of 2 -fluoro-3-methyl-nitrobenzene and 3 g of 4-bromo-aniline in the presence of 2.09 g of potassium tert-butanolate in 20 mL of DMSO. Yield: 68% H NMR (CDCl 3, 300 MHz) d (ppm): 8.15 (broad s, 1 H), 7.96 (d, 1 H), 7.07-7.51 (aromatic mass, 4H), 6.61 (d, 2H) 2.09 (s, 3H) HPLC: 90% MS: MH + 307/309.

Step 2: N2- (4-bromo-phenyl) -3-methyl-benzene-1,2-diamine The product (2.2 g) is obtained according to the method of step 2 of Example 1, using 2.44 g of the derivative previous as a starting product and 9 g of tin chloride hydrate in 30 mL of ethanol. Yield: quantitative 1 H NMR (CDCIa, 300 MHz) d (ppm): 7.22 (s, 1 H), 7.02 (t, 1 H), 6.45 (m, 3 H), 6.43 (d, 2 H), 4.98 (s broad) , 1 H), 2.14 (s, 3H) HPLC. 99% MS: MH + 277/279.

Step 3: (4-bromo-phenyl) - (2-methyl-6-piperidin-1-yl-phenyl) -amine The product (2 g) is obtained according to the method of step 3 of Example 4, using 2.2 g of the previous derivative as a starting product, 1.08 mL of dibromopentane and 3.3 mL of DIPEA in 40 mL of toluene. Yield: 73% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.26 (m, 2 H), 7.03 (t, 1 H), 6.94 (d, 2 H), 6.56 (d, 2 H), 6.14 (s broad) , 1 H), 2.70 (m, 4H), 2.10 (s, 3H), 1.55 (m, 6H) HPLC: 99% MS: MH + 345/347.

Step 4: (4'-methoxy-biphenyl-4-yl) - (2-methyl-6-piperidin-1-yl-phenyl) -amine The product (248 mg) is obtained according to the method of step 4 of Example 11, using 300 mg of the previous derivative as a starting product, 198 mg of phenylboronic acid, 50 mg of tetracis palladium, 110 mg of lithium chloride in the presence of 2.17 mL of an M solution of calcium carbonate in 6 mL of a methanol / toluene mixture (1: 1). Yield: 76% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.48 (d, 2 H), 7.39 (d, 2 H), 6.92-7.03 (m, 5 H), 6.74 (d, 2 H), 6.24 (s) broad, 1 H), 3.84 (s, 3H), 2.74 (m, 4H), 2.16 (s, 3H), 1.56 (m, 6H) HPLC: 81% MS: MH + 373.

Step 5: N- (4'-methoxy-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine (u) The product (92 mg) is obtained according to the method of step 4 of Example 1, using 247 mg of the previous derivative as an initial product and 265 mg of sodium nitrite in 3 mL of acetic acid, leading to the nitroso intermediate, which is reduced with 101 mg of hydride of lithium and aluminum (4 equivalents) in 5 mL of tetrahydrofuran with reflux. Yield: 35% 1 H NMR (CDC, 300 MHz) d (ppm): 7.48 (d, 2H), 7.38 (d, 2H), 7.17 (t, 1 H), 6.86-7.03 (m, 6H), 4.90 ( s broad, 2H), 3.83 (s, 3H), 2.95 (m, 2H), 2.69 (m, 2H), 2.1 1 (s, 3H), 1.51-1.66 (m, 6H) HPLC: 95% MS: MH + 388.

Step 6: methyl 5-bromo-2-methoxy-4- [N- (4'-methoxybiphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethylbenzoate The product (24 mg) is obtained according to the method of step 3 of Example 6, using 92 mg of the previous hydrazine and 79 mg of the acid of preparation 2 in the presence of 50 mg of EDCI and 35 mg of HOBt in 2.5 mL of dimethylformamide. Yield: 15% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 8.00 (s, 1 H), 6.85-7.51 (aromatic mass, 10 H), 6.62 (d, 2 H), 3.72-3.88 (m, 1 1 H), 2.81 (m, 2H), 2.43 (m, 5H), 1.25-1.56 (m, 6H) HPLC: 87% MS: MH + 672/674.

Step 7: 5-Bromo-2-methoxy-4- [N- (4'-methoxy-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrochloride hydrazine-carbonylmethyl-1-b (28) The product (13 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 52% Elemental analysis calculated for C35H36BrN3O5.1 HCI. .5H2O: C, 58.22; H, 5.58; N, 5.82. Found: C, 58.06; H, 5.63; N, 5.58. HPLC: 82% MS: MH + 658/660.

EXAMPLE 29 5-Bromo-4-fN-cyano-phene-N- (2-metii-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-2-methoxy-benzoic acid hydrochloride (29) Step 1: N- (2-methyl-6-nitro-phenyl) -hydrazine-tert-butyl carboxylate To 250 mg of 2-fluoro-3-methyl-nitrobenzene in 5 ml of DMSO, 1065 g of tert. -butoxycarbonylhydrazine (5 equivalents). Everything was brought to 100 ° C for 10 minutes under microwave heating. The medium was hydrolyzed and then extracted with ethyl acetate several times. The organic phases were collected, dried over magnesium sulfate, filtered and evaporated under reduced pressure leading to a residue, which was purified by chromatography on silica gel (cyclohexane / ethyl acetate: 80/20). 342 mg of the product corresponding to the expected product were obtained. Yield: 80% H NMR (CDCl 3, 250 MHz) d (ppm): 7.86 (d, 1 H), 7.35 (d, 1 H), 6.97 (t, 1 H), 6.40 (broad s, 1 H), 1.34 (broad s, 9H) HPLC: 98%.

Stage 2j N- (4-cyano-phenyl) -N- (2-methyl-6-nitro-phenyl) -hydrazinecarboxylate of tert-butyl A 1.5 g of the product obtained in the previous step in 10 mL of dichloromethane were added to 0 ° C, 2.45 g of activated manganese oxide (5 equivalents). Everything was stirred at room temperature for 30 minutes until the complete disappearance of the starting product (tracked by TLC). The oxidized intermediate was filtered over celite, rinsed with dichloromethane and then concentrated under reduced pressure, any other form of purification. The tert-butyl azocarboxylate derivative thus obtained was immediately taken in 10 mL of methanol, to which 1.27 g of 4-cyanophenylboronic acid (1.6 equivalents) and 54 mg of copper acetate hydrate (0.05 equivalents) were successively added. ). All was refluxed for 24 hours until the complete disappearance of the oxidized intermediate. The reaction medium was hydrolyzed and then extracted with ethyl acetate several times. The organic phases were washed with water, then with brine and finally dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue obtained was purified by chromatography on silica gel (dichloromethane / cyclohexane: 1/1), yielding 1.13 g of the expected product. Yield: 57% 1 H NMR (CDCl 3> 300 MHz) d (ppm): 7.98 (d, 1 H), 7.67 (t, 2 H), 7.49 (m, 3 H), 6.60 (d, 2 H), 2.49 (s) , 3H), 1.48 (s, 9H) HPLC: 78%.

Step 3 N- (2-amino-6-methyl-phenyl) -N- (4-cyano-phenyl) -hydrocarboxylic acid tert-butyl 982 mg of the product were obtained by catalytic hydrogenation in the presence of 110 mg of 5% of palladium on carbon in 50 mL of ethanol from 1.13 g of the product obtained in the previous stage. Yield: 97% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.48 (d, 2H), 7.09 (m, 1 H), 6.62 (m, 4H), 4.78 (broad s, 2H), 4.40 (s) broad, 1 H), 2.02 (s, 3H), 1.50 (s, 9H) HPLC: 80%.

Step 4: N- [2- (5-bromo-pentanoylamino) -6-methylphenyl-N- (4-cyano-phenyl-hydrazinocarboxylate of tert-butyl A 980 mg of the product obtained from the previous step in 8 mL of dichloromethane in the In the presence of 820 pl_ of DIPEA (2 equivalents), 388 μl of 5-bromovaleryl chloride was added dropwise at room temperature After 20 minutes, the crude reaction product was hydrolyzed by a hydrochloric acid solution. N, extracted with dichloromethane several times The organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure leading to 1.4 g of the expected product Yield (estimate): 96% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 10.03 (s, 1 H), 8.28 (d, 1 H), 7.49 (d, 1 H), 7.34 (t, 2 H), 6.95-7.20 (m, 3 H), 3.43 (m , 2H), 3.30 (t, 2H), 2.51 (t, 2H), 2.34 (m, 2H), 2.07 (s, 3H), 1.53 (s, 9H) HPLC: 56%.

Step 5: N- (4-cyano-phenyl) -N- [2-methyl-6- (2-oxopiperidin-1-yl) -phenyl-1-hydrazinocarboxylic acid tert -butyl ester To 1.4 g of the product previously obtained in 5 mL of DF, 225 mg of sodium hydride (2 equivalents) were added at 0 ° C. After 20 minutes at room temperature, the crude reaction product was hydrolyzed and then extracted with ethyl acetate several times. The collected organic phases were washed with water and then with brine and finally dried over magnesium sulfate, filtered and concentrated under reduced pressure leading to 1.1 g of the expected product. Performance (estimate): quantitative.

Step 6: N- (4- (amino-methyl) -phenyl-1 N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinecarboxylic acid tert -butyl A 440 mg of the product obtained from the previous stage in 3 mL of THF, 493 pL of dimethyl borane sulfide (5 equivalents) was added, and the whole was refluxed for 1 hour.The crude reaction product was hydrolyzed and extracted with ethyl acetate several times. were collected, washed with water and then with a 1 N hydrochloric acid solution The aqueous phase was taken with a saturated sodium bicarbonate solution and then extracted with ethyl acetate.The organic phases were collected, dried over sulphate of magnesium were filtered and concentrated under reduced pressure leading to 308 mg of the expected product Yield (estimate): 71%.

Step 7: N- [4- (Acetylamine-methyl) phenin-N- (2-methyl-6-piperidin-1-yl-phenyl-hydrazinocarboxylate tert -butyl) To a solution of 300 mg of the product obtained from the The previous step in 10 mL of tetrahydrofuran under an inert atmosphere was added with 267 μ DIPEA (2 equivalents) and 76 μ D acetic anhydride (1.4 equivalents), all were stirred at room temperature for 30 minutes until the complete disappearance of the starting product (tracked with TLC) The reaction medium was taken up in ethyl acetate, hydrolyzed with a 1 N hydrochloric acid solution and extracted several times. Sodium bicarbonate solution was added to a pH of 8 and extracted with ethyl acetate.The organic phases were collected, dried over magnesium sulfate, filtered and evaporated under reduced pressure.The residue obtained was purified by gel chromatography. silica (ether and then dicl oromethane), leading to 165 mg of the expected product. Yield (estimate): 51% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 8.92 (broad s, 1 H), 7.18 (d, 1 H), 7.07 (m, 4 H), 6.62 (d, 2 H) , 5.60 (broad s, 1 H), 4.32 (m, 2H), 2.80 (m, 2H), 2.65 (m, 2H), 2.31 (s, 3H), 2.01 (s, 3H), 1.60 (m, 6H) ), 1.44 (s, 9H).

Step 8: 4- (N- [4- (Acetylaminomethyl) -phenill-N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-bromo-2-methoxy-benzoate methyl A A solution of 51 mg of the acid obtained in Preparation 2 (2 equivalents) in 2 mL of dichloromethane was added with 14.4 pL of oxalyl chloride (2 equivalents) and 1 drop of dimethylformamide, all stirred for 20 minutes at room temperature. and then evaporated under reduced pressure.The acid chloride thus obtained was taken up again in 1 mL of acetonitrile, a solution of 38 mg of the previous ester in 1 mL of acetonitrile and 1 mL of hydrochloric acid was successively added to it. N in dioxane.The whole was placed for 10 minutes under heating with microwaves at 100 ° C. The reaction medium was hydrolyzed and then extracted with ethyl acetate several times.The aqueous phase was then basified with a 1N sodium hydroxide solution. and extracted with ethyl acetate and then with dichloromethane The organic phases were collected, dried over magnesium sulfate, filtered and then evaporated under reduced pressure. With chromatography on silica gel of the residue (dichloromethane / ethanol: 98/2), 18 mg of the expected product can be obtained. Yield: 34% H NMR (CDCl 3, 300 MHz) d (ppm): 10.05 and 9.83 (broad 2s, 1 H), 7.99 (s, 1 H), 7.18 (m, 2H), 7.05 (m, 4H), 6.52 (d, 2H), 5.67 (broad s, 1 H), 4.29 (d, 2H), 3.88 (s, 3H), 3.73 (m, s, 2H), 3.71 (s, 3H), 2.75 (m, 2H), 2.40 (m, 2H), 2.37 (s, 3H), 1.98 (s, 3H), 1.46 (m, 6H) HPLC: 97.3% MS: MH + 637/639.

Stage 9: 4- Hydrochloride. { N-f4- (Acetylamino-methyl) -phenyl-N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonyl-methyl) -5-bromo-2-methoxy-benzoic acid (29) The product (13.8 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained with the previous step. Yield: 75% HPLC: 91% MS: MH + 623/625.

EXAMPLE 30 4- [N- (4-Benzoyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-5-bromo-2-methoxy-benzoic acid hydrochloride (30) Step 1: (4-benzoyl-phenyl) - (2-nitro-phenyl) -amine The product (770 mg) is obtained according to the method of step 1 of Example 4, using 1.5 mL of 2-fluoro-nitrobenzene and 4.2 g of 4-aminobenzophenone in the presence of 2.54 g of potassium tert-butanolate in 40 mL of DMSO. Yield: 17% HPLC: 86% MS: MH + 319.

Step 2: N- (4-Benzoyl-phenyl) -benzene-1,2-diamine The product (880 mg) is obtained according to the method of step 2 of Example 1, using 770 mg of the previous derivative as a product initial and 2.73 g of tin chloride hydrate in 15 mL of ethanol. Yield: quantitative 1 H NMR (CDCl 3, 300 MHz) d (ppm): 7.74 (t, 4 H), 7.36-7.53 (m, 3 H), 7.13 (m, 2 H), 6.70-6.85 (m, 4 H), 5.63 ( s broad, 1 H), 3.80 (broad s, 1 H) HPLC: 82% MS: MH + 289.

Step 3: (4-benzoyl-phenyl) - (2-piperidin-1-phenyl) -amine The product (530 mg) is obtained according to the method of step 3 of Example 4, using 697 mg of the derivative previous as a starting product, 330 pL of dibromopentane and 1.01 mL of DIPEA in 15 mL of toluene. Yield: 62% H NMR (CDCl 3, 300 MHz) d (ppm): 7.80 (dd, 4H), 7.45-7.56 (m, 4H), 6.96-7.18 (m, 6H), 2.84 (m, 4H), 1.60 -1 .74 (m, 6H) HPLC: 100% MS: MH + 357.

Step 4: N- (4-benzoyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine (v) To a solution of 100 mg of the previous compound in 10 mL of DMF was added 14 mg of sodium hydride (1.2 equivalents), and everything was stirred at room temperature for 45 minutes. 2.3 mL of a fresh prepared 0.15 M solution was added in monochloramine ether (1.2 equivalents) (J. Org. Chem. 2004, 69, 1368-1371). After 5 minutes, the medium was treated with a saturated solution of Na2S203, taken again with water and then extracted with ether several times. The organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue obtained was purified by chromatography on silica gel (petroleum ether / ethyl acetate: 95/5), yielding 75 mg of the expected product. Yield: 72% 1 H NMR (CDCIa, 250 MHz) d (ppm): 7.73 (d, 4H), 7.48 (m, 3H), 7.25 (m, 2H), 7.05-7.17 (m, 4H), 4.89 (s) broad, 2H), 2.91 (m, 4H), 1.57 (m, 6H) HPLC: 100% MS: MH + 372.

Step 5: methyl 4-rN- (4-benzoyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl-5-bromo-2-methoxy-benzoate The product (83 mg) is obtained from according to the method of step 3 of Example 6, using 70 mg of the above hydrazine and 64 mg of the acid of preparation 2 in the presence of 41 mg of EDCI and 28 mg of HOBt in 1.5 ml_ of dimethylformamide. Yield: 66% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 9.36 (broad s, 1 H), 7.99 (s, 1 H), 6.80-7.76 (aromatic mass, 14H), 3.89 (s, 3H) , 3.80 (s, 2H), 3.72 (s, 3H), 2.75 (m, 4H), 1.54 (m, 6H) HPLC: 100% MS: MH + 656/658.

Step 6: 4- [N- (4-Benzoyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazocarbonylmethyl-5-bromo-2-methoxy-5-benzoic acid hydrochloride The product (31 mg) is obtained according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 37% Elemental analysis calculated for C34H32BrN3O5.I HCLI .5H2O: C, 57.84; H, 5.14; N, 5.95. Found: C, 58.04; H, 5.13; N, 5.55. HPLC: 100% MS: MH + 642/644.

EXAMPLE 31 5-Bromo- -fN-cyano-phenyl] -N- (2-methyl-6-p-perpentin-1-yl-phenyl) -hydrazinocarbonylmethyl-2-methoxy-benzoic acid hydrochloride (31 ) Step 1: N- (4-cyano-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinecarboxylic acid tert -butyl ester To 280 mg of the product obtained in step 5 of the Example 29 in 2 mL of tetrahydrofuran, 3.3 mL of a 1 M solution of borane in tetrahydrofuran (5 equivalents) was added. All was refluxed for 3 hours. The crude reaction product was poured into a 1N hydrochloric acid solution and extracted with ethyl acetate several times. The aqueous phase was basified with a 1 N sodium hydroxide solution and extracted with dichloromethane. The different organic phases were collected, they were washed with water and then with a saturated solution of NaCl, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue obtained was purified by chromatography on silica gel (dichloromethane / ethyl acetate: 98/2), yielding 82 mg of the expected product. Yield: 30% 1 H NMR (CDCl 3, 300 MHz) d (ppm): 8.92 (broad s, 1 H), 7.46 (d, 2H), 7.21 (m, 1 H), 7.06 (t, 2H), 6.72 (m, 2H), 2.74 (m, 4H), 2.29 (s, 3H), 1.60 (m, 6H), 1.43 (s, 9H).

Step 2: 5-bromo-4-IN- (4-cyano-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine-carbonyl-methyl-2-methoxybenzoate Methyl The product (32 mg) is obtained according to the method of step 8 of Example 31, using 42 mg of the product obtained in the previous step as a substrate and 94 mg of the acid of preparation 2 as a cosubstrate. Yield: 56% H NMR (CDCl 3, 300 MHz) d (ppm): 9.78 (s, 1 H), 7.98 (s, 1 H), 7.45 (d, 2 H), 7.24 (m, 2 H), 7.01 (m , 2H), 6.62 (m, 2H), 3.88 (s, 2H), 3.37 (s, 6H), 2.70 (m, 2H), 2.45 (m, 2H), 2.35 (s, 3H), 1.42 (m, 6H) HPLC: 94% MS: MH + 591/593.

Step 3: Bromo-4- [N- (4-cyano-phenyl) -N- (2-methyl-6-piperidin-1-ylphenyl) -hydrazinocarbonylmethyl-2-methoxy-benzoic acid hydrochloride (31) The product (16.4 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 49% HPLC: 98% MS: MH + 577/579.

EXAMPLE 32 4- [N- (4'-Acetyl-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethin-5-bromo-2-hydrochloride methoxy-benzoic (32) Step 1: (4'-Acetyl-biphenyl-4-yl) - (2-methyl-6-piperidin-1-yl-phenyl) -amine The product (1.35 g) is obtained according to the method of step 4 of Example 11, using 2.6 g of the derivative obtained in step 3 of Example 28 as a starting product, 248 g of 4-acetyl-phenylboronic acid , 307 mg of [1, 1 '-bis (diphenylphosphino) ferrocene] -dichloropalladium (II) and 4.58 g of cesium fluoride in 150 mL of dioxane. Yield: 47% 1 H NMR (CDCl 3, 200 MHz) d (ppm): 7.98 (d, 2 H), 7.65 (d, 2 H), 7.51 (d, 2 H), 7.03 (m, 3 H), 6.76 (d, 2 H) ), 6.29 (s broad, 1 H), 2.75 (m, 4H), 2.63 (s, 3H), 2.17 (s, 3H), 1.58 (m, 6H) MS: MH + 385.

Step 2: 4 '- (2-methyl-n, 31-dithian-2-yl) -biphenyl-4-ill- (2-methyl-6-piperidin-1-yl-phenyl) -amine To one solution of 788 mg of the derivative obtained in the previous step in 14 mL of dichloromethane, 260 pL of propandithiol (1.25 equivalents) and 380 pL of boron trifluoride complexed with diethyl ether were added successively. Everything was stirred for 2 days at room temperature until the disappearance of the starting product. The reaction medium was poured into a 2 N sodium hydroxide solution and then extracted with dichloromethane several times. The organic phases were washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure leading to 970 mg of the expected product. Yield: quantitative H NMR (CDCl 3, 200 MHz) d (ppm): 7.96 (d, 2H), 7.58 (d, 2H), 7.48 (d, 2H), 7.03 (m, 3H), 6.77 (d, 2H) , 6.26 (broad s, 1 H), 2.76 (m, 8H), 2.18 (s, 3H), 1.95 (m, 2H), 1.84 (s, 3H), 1.54 (m, 6H) Step 3: N-f4 '- (2-methyl- [.31-dithian-2-yl) -biphenyl-4-in-N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine ( w) The product (835 mg) is obtained according to the method of step 4 of Example 1, using 970 mg of the previous derivative as an initial product and 1.11 g of sodium nitrite in 6 mL of acetic acid, leading to the intermediate nitrous, which is reduced by 8.2 mL of a 1 M solution of lithium aluminum hydride in ether (4 equivalents) in 8 mL of ether with reflux. Yield: 83% 1 H NMR (CDCl 3, 200 MHz) d (ppm): 7.92 (d, 2 H), 7.57 (d, 2 H), 7.46 (d, 2 H), 7.19 (d, 1 H), 7.05 (t, 2H), 6.90 (d, 2H), 2.70-2.95 (m, 8H), 2.12 (s, 3H), 1.96 (m, 2H), 1.82 (s, 3H), 1.65 (m, 6H).

Step 4: 5-bromo-2-methoxy-4- (N- [4 '- (2-methyl- [1 .31ditian-2-n-biphenyl-4-yl-N- (2-methyl-6- methyl piperidin-1-yl-phenyl) -hydrazanocarbonyl The product (637 mg) is obtained according to the method of step 3 of Example 6, using 600 mg of the previous hydrazine and 406 mg of the acid of the preparation 2 in the presence of 257 mg of EDCI and 181 mg of HOBt in 4 ml_ of dimethylformamide Yield: 67% 1 H NMR (CDCl 3, 200 MHz) d (ppm): 9.87 (broad s, 1 H), 7.96 (m, 3H), 7.50 (m, 5H), 7.20 (d, 1 H), 7.03 (m, 2H), 6.65 (d, 2H), 3.88 (s, 3H), 3.70 (2s, 5H), 2.75 (m, 8H), 2.44 (s, 3H), 1.97 (m, 2H), 1.81 (s, 3H), 1.25-1.55 (m, 6H) MS: MH + 774/776.

Step 5: 4-rN- (4'-Acetyl-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonyl-methylene-5-bromo-2-methoxy Methyl-benzoate To a solution of 30 mg of the derivative obtained in the previous step in 100 μl of a tetrahydrofuran / water mixture (1: 1), 17 mg of mercury (II) oxide was added sequentially. (2 equivalents) and 10 μ? of boron trifluoride complexed with ether (2 equivalents). Everything was stirred at room temperature for 1 hour, until the complete disappearance of the starting product. The reaction medium was poured into a 2 M sodium bicarbonate solution and then extracted with ethyl acetate several times. The organic phases were washed with a saturated solution of sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure. Chromatography on silica gel (cyclohexane / ethyl acetate: 70/30), was able to isolate 19.5 mg of the desired product. Yield: 73% 1 H NMR (CDCl 3, 200 MHz) d (ppm): 9.88 (broad s, 1 H), 7.97 (m, 3 H), 7.62 (d, 2 H), 7.48 (d, 2 H), 7.21 (d , 1 H), 7.03 (m, 2H), 6.67 (d, 2H), 3.89 (s, 3H), 3.77 (2s, 5H), 2.80 (m, 2H), 2.62 (s, 3H), 2.42 (m + s, 5H), 1.30-1.50 (m, 6H) MS: MH + 684/686.

Step 6: 4-fN- (4'-Acetyl-biphenyl-4-tl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazylcarbonylmethyl-5-bromo-2-hydrochloride -methoxy-benzoic acid (32) The product (15 mg) is obtained as a hydrochloride form according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 34% H NMR (DMSO, 400 MHz) d (ppm): 7.99 (m, 3H), 7.37-7.81 (m, 7H), 7.37 (s, 1 H), 6.78 (m, 2H), 4.24 (d, 1 H), 4.03 (d, 1 H), 3.79 (s, 3H), 3.20-3.60 (m, 4H), 2.57 (s, 3H), 2.28 (s, 3H), 1.51-1.86 (m, 6H) HPLC: 96% MS: MH + 670/672.

EXAMPLE 33 5-Bromo-2-methoxy-4-rN- (4'-methoxy-2-methyl-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl) hydrochloride ) -hydrazinecarbonylmethane-benzoic acid (33) Step 1: (4-bromo-3-methyl-phenyl) - (2-methyl-6-nitrophenyl) -amine The product (3.90 g) is obtained according to the method of step 1 of Example 4, using 2.78 g. of 2-fluoro-3-methyl-nitrobenzene and 5 g of 4-bromo-3-methyl-aniline in the presence of 3.22 g of potassium tert-butanolate in 70 ml of DMSO. Yield: 68% 1 H NMR (CDCl 3, 200 MHz) d (ppm): 8.15 (broad s), 7.96 (d, 1 H), 7.43 (d, 1 H), 7.37 (m, 1 H), 7.10 (t , 1 H), 6.65 (m, 1 H), 6.42 (dd, 1 H), 2.33 (s, 3H), 2.10 (s, 3H).

Step 2: N2- (4-bromo-3-methyl-phenyl) -3-methyl-benzene-1,2-d-amines The product (3.2 g) is obtained according to the method of step 2 of Example 1 , using 3.9 g of the previous derivative as a starting product and 13.7 g of tin chloride hydrate in 60 ml_ of ethanol. Yield: 90% 1 H NMR (CDCl 3> 200 MHz) d (ppm): 7.29 (d, 1 H), 7.03 (t, 1 H), 6.68 (d, 2 H), 6.47 (d, 1 H), 6.28 ( dd, 1H), 4.94 (s broad, 1 H), 2.29 (s, 3H), 2.16 (s, 3H).

Step 3: (4-bromo-3-methyl-phenyl) - (2-methyl-6-piperidin-1-yl-phenyD-amine The product (3.21 g) is obtained according to the method of step 3 in the Example 4, using 3.2 g of the previous derivative as a starting product, 1.50 ml_ of dibromopentane and 4.30 ml of DIPEA in 50 ml_ of toluene Yield: 81% 1 H NMR (CDCl 3) 200 MHz) d (ppm): 7.28 (d , 1 H), 7.04 (m, 3H), 6.58 (d, 1 H), 6.41 (dd, 1 H), 6.13 (s broad, 1 H), 2.72 (m, 4H), 2.32 (s, 3H) , 2.11 (s, 3H), 1.57 (m, 6H).

Step 4: (4'-methoxy-2-methyl-biphenyl-4-yl) - (2-methyl-6-piperidin-1-yl-phenyl-amine) The product (1921 g) is obtained according to the method of step 4 of Example 11, using 3 g of the previous derivative as a starting product, 1904 g of 4-methoxy-phenyl boronic acid, 392 mg of tetracis palladium, 1062 g of lithium chloride in the presence of 9 mL of a solution 1 M sodium carbonate in 60 mL of a methanol / toluene mixture (1: 1) Yield: 60% H NMR (CDCl 3, 200 MHz) d (ppm): 7.28 (d, 2H), 7.03 (m, 6H), 6.59 (m, 2H), 6.26 (s broad, 1 H), 3.86 (s, 3H), 2.77 (m, 4H), 2.25 (s, 3H), 2.20 (s, 3H), 1.63 (m , 6H).

Step 5: N- (4'-methoxy-2-methyl-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl-hydrazine (x) The product (385 mg) was obtained according to the method of step 4 of Example 1, using 490 mg of the previous derivative as an initial product and 515 mg of sodium nitrite in 4 mL of acetic acid, leading to the nitroso intermediate, which is reduced with 4.8 mL of a 1 M solution of lithium aluminum hydride in ether (4 equivalents) in 4.5 mL of ether with reflux Yield: 80% 1 H NMR (CDCl 3, 200 MHz) d (ppm): 6.90-7.27 (aromatic mass, 10H) , 6.78 (broad s, 1 H), 6.57 (d, 1 H), 3.83 (s, 3H), 2.92 (m, 4H), 2.22 (s, 3H), 2.12 (s, 3H), 1.68 (m, 4H), 1.53 (m, 2H).

Step 6: 5-bromo-2-methoxy-4- [N- (4'-methoxy-2-methyl-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl) - methyl hydrazinocarbonylmethyl-1-benzoate The product (450 mg) is obtained according to the method of step 3 of Example 6, using 381 mg of the pre-hydrazine and 316 mg of the acid of preparation 2 in the presence of 200 mg of EDCI and 144 mg of HOBt in 3.8 mL of dimethylformamide.

Yield: 69% 1 H NMR (CDCl 3, 200 MHz) d (ppm): 10.06 and 9.84 (broad 2s, 1 H), 8.01 (s, 1 H), 7.20 (m, 4H), 6.89-7.02 (m, 5H) ), 6.50 (s, 1 H), 6.38 (d, 1 H), 3.89 (s, 3H), 3.84 (s, 3H), 3.76 (m, 2H), 3.72 (s, 3H), 2.80 (m, 2H), 2.45 (m, 5H), 2.18 (s, 3H), 1.30-1.58 (m, 6H).

Step 7: 5-Bromo-2-methoxy-4- [N- (4'-methoxy-2-methyl-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl) hydrochloride phenyl) -hydrazinocarbonylmethyl-1-benzoic acid (33) The product (264 mg) is obtained as a hydrochloride according to the method of step 6 of Example 2, using as a substrate the product obtained in the previous step. Yield: 67% 1 H NMR (DMSO, 200 MHz) d (ppm): 1 1.79 (broad s, 1 H), 1 1.44 (broad s, 1 H), 7.96 (d, 1 H), 7.81 (s, 1 H), 7.70 (m, 2H), 7.34 (s, 1 H), 7.23 (d, 2H), 6.99 (d, 1 H), 6.75 (d, 2H), 6.44 (s, 1 H), 6.42 ( d, 1 H), 4.10 (m, 2H), 3.78 (s, 6H), 3.40 (m, 4H), 2.27 (s, 3H), 2.19 (s, 3H), 1.53-1.86 (m, 6H) HPLC : 98.5% MS: MH + 672/674.

Results of the biological activity The activity of the molecules against the papilloma virus can be evaluated in different in vitro and cellular tests, such as those described by Chiang et al. (1992), Proc. Nati Acad. Sci. USA, 89: 5799-5803 or in addition by White at al. (2003), Journal of Biological Chemistry, 278: 26765-26772.

EXAMPLE 34 Pharmacological studies of the compounds of the invention in cellular tests for replication of HPV viral DNA These tests measure the replication of viral genomic DNA in human cells. They are based on the cotransfection of a reporter vector that contains an origin (ori) of viral replication and of expression vectors that encode HPV E1 and E2 proteins. With them, it is possible to follow all the biological functions of E1 and E2 required for the replication of the HPV genome. A reporter "replicon" vector containing the origin of the viral replication of HPV1 / HPV6 (also called LCR, which carries the sites for the binding of the HPV E1 and E2 proteins) and the gene encoding the luciferase of the firefly under the transcriptional control of the SV40 promoter. It was verified that the presence of the HPV origin of replication does not have any transcriptional effect on the expression of the luciferase gene, this in the presence or absence of the viral E1 or E2 proteins. The co-transfection of this replicon vector and of the vectors to express the HPV E1 and E2 proteins leads to an increase in the luciferase activity that depends on the presence of E1 and E2 and expresses the increase in the number of reporter vectors. This is due to the activity of the viral E1 and E2 proteins that allow the replication, in mammalian cells, of this replicon vector that contains a viral origin of replication. The chemical compounds were evaluated for their activity, inhibiting the viral replication dependent on E1 and E2 of HPV1 / HPV6 in these cellular tests., by contransfection, in human cell lines derived from renal or cervical epithelial carcinoma cells, from the reporter replicon vector and pairs of E1 and E2 expression vectors HPV1 1 / HPV6. Several doses of the compounds were incubated for 2-6 days after transfection in the cell medium and the luciferase activity was determined by means of a luminometer in order to evaluate the Cl50 of the compounds in the replication of the HPV genome. . All the compounds shown in the previous examples inhibit the E1 and E2-dependent replication of HPV1 / HPV6 in cells with an IC50 of less than 20 μ ?. Preferred compounds are those for which the IC50 may be less than 750 nM. With complementary cellular tests, it was possible to show that the compounds shown in the previous examples inhibit the E1 / E2 interaction of HPV11 HPV6.

Claims (2)

1. NOVELTY OF THE INVENTION CLAIMS 1. - The compounds of formula (I): (1) as well as its stereoisomers, wherein: d represents a saturated or unsaturated, branched or linear hydrocarbon chain or bond, comprising 1-4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, G2 represents a group , wherein: R represents a hydrogen atom, an alkyl group, haloalkyl, or a prodrug radical, such as a carbamate, acetyl, dialkylaminoethyl or -CH2-O-CO-Alk, G represents a bond or a chain saturated or unsaturated hydrocarbon, linear or branched, comprising 1 -4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, · W represents an oxygen atom, sulfur or NH, Ri and R2 and they are identical or different, they each represent a group selected from a hydrogen atom, a halogen atom, a hydroxyl group, thio, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, monoalkylamino, dialkylamino, cycloalkyl, alkyl or haloalkyl, R3 represents an acid group or a radical of the prodrug of the acid function such as an ester, or in addition a bioester of the acid function, such as a tetrazole, phosphonate, phosphonamide, sulfonate or sulfonamide, A represents an aryl group, cycloalkyl it, cycloalkenyl or a heterocycle, each optionally substituted, and B represents an aryl group or a 6-membered heterocycle, each optionally substituted, as well as its pharmaceutically acceptable salts. 2 - The compounds according to claim 1, further characterized in that A is substituted with one or two groups, either identical or different, selected from: · a hydrogen atom, a halogen atom, · an alkoxy, alkylthio group, haloalkoxy, haloalkylthio, hydroxyl, thio, cyano, amino, monoalkylamino or dialkylamino, · a group -SOnR ', -COR', -C02R \ -OCOR ', -CONR'R ", -NR'COR" or -NR'SO2R ", wherein R 'and R" each independently represents one hydrogen atom, one alkyl group, haloalkyl, and n has the value of 1 or 2, · an alkyl or haloalkyl group, the alkyl group being substituted optionally with a cyano, amino, monoalkylamino, dialkylamino or acylamino group, an aryl, arylalkyl, -X-aryl, -X-arylalkyl or -Alk-X-aryl group, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, each substituted on the aryl portion with one or two substituents, either identical or dif Examples, selected from: a hydrogen atom or a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkylamino or dialkylamino group, acid, ester, amide, mono or dialkylamide, a group -SOnR "-COR", -CO2R ', -OCOR', -CONR'R ", -NR'COR" or -NR'SO2R ", wherein R 'and R" each represents independently of one another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, · a heterocycle group, -Alk-heterocycle, -X-heterocycle, -X-Alk-heterocycle or -Alk-X -heterocycle, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, each one optionally substituted on the heterocycle portion with one or two substituents, either identical or different, selected from: a hydrogen atom or a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl group, cyano, acyl, amino, monoalk ilo or dialkylamino, acid, ester, amide, mono or dialkylamide, or a group -SOnR \ -COR ', -CO2R \ -OCOR', -CONR'R ", -NR'COR" or -NR'SO2R ", in where R 'and R "each represents independently of one another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, · a cycloalkyl group, -Alk-cycloalkyl, cycloalkenyl, -Alk- cycloalkenyl, -X-cycloalkyl, -X-Alk-cycloalkyl, -X-cycloalkenyl, -X-Alk-cycloalkenyl, -Alk-X-cycloalkyl, -Alk-X-cycloalkenyl, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, each optionally substituted in the cyclic portion with one or two substituents, either identical or different, selected from: a hydrogen atom or a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide, or oxo or, a group -SOnR ', -COR', -CO2R ', -OCOR', -CONR'R ", -NR'COR" or -NR'SO2R ", wherein R 'and R" each represents independently of one another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, and Gi, G2, Ri, R2, R3 and B are in accordance with claim 1. 3. The compounds according to claim 1 or 2, further characterized in that B is an aryl a 6-membered heterocycle, substituted on the ortho position with a R4 group and substituted optionally with a group R5l wherein: R4 represents: an alkyl group, -NHAIk, -NAIkAlk ', -NHcycloalkyl or -NAIkcycloalkyl, Alk and Alk' being identical or different, a cycloalkyl, cycloalkenyl, N-cycloalkyl or N- group cycloalkenyl, each optionally substituted with one or two substituents, either identical or different, selected from a hydrogen atom, a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano group, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide, oxo or -X-aryl, and wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, SO2-, -CO- or -CONH-, or? an aryl group optionally substituted with one or two substituents, either identical or different, a hydrogen atom, a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino group , monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide or -X-aryl, wherein X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, · R5 represents:? a hydrogen atom or a halogen atom, a hydroxyl group, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, amino, monoalkylamino, dialkylamino, -NHacyl, cyano, acyl, acid, ester, amide, monoalkylamide or dialkylamide, an alkyl group or haloalkyl, the alkyl group may be substituted with a cyano, hydroxyl, alkoxy, acid or ester group, and a group -SOnAlk, -SOnNH2, -SOnNHAIk or -SOpNAIkAlk ', where n has the value of 1 or 2, and Alk and Alk 'are either identical or different, or a piperidine, oxopiperidine, morpholine group or in addition a piperazine group optionally substituted with an alkyl or acyl group, and Gi, G2, R- ?, R2, R3 and A are in accordance with claim 1 or 2. 4. The compounds according to any of claims 1 to 3, further characterized in that: G1 represents a saturated or unsaturated, straight or branched hydrocarbon chain or bond, comprising 1-4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, G2 represents a group , wherein: R represents a hydrogen atom, an alkyl group, haloalkyl, or a radical of the prodrug, such as carbamate, acetyl, dialkylaminoethyl or -CH2-O-CO-Alk, G represents a bond or a chain of saturated or unsaturated, linear or branched hydrocarbon, comprising 1 -4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, and · W represents an oxygen atom, sulfur or NH, Ri and R2 and they are identical or different, they each represent a group selected from a hydrogen atom, a halogen atom, a hydroxyl group, thio, alkoxy, haloalkoxy, alkylthio, haloalkylthio, amino, monoalkylamino, dialkylamino, cycloalkyl, alkyl or haloalkyl, R3 represents an acid group or a radical of the prodrug of the acid function such as an ester, or in addition a bioester of the acid function, such as a tetrazole, phosphonate, phosphonamide, sulfonate or sulfonamide, A represents an aryl or heterocyclic group it, each being optionally substituted with one or two groups, either identical or different, selected from: a hydrogen atom, a halogen atom, an alkoxy, alkylthio, haloalkoxy, haloalkylthio, hydroxyl, thio, cyano group, amino, monoalkylamino or dialkylamino, · a group -SOnR ', -COR', -C02R \ -OCOR ', -CONR'R ", -NR'COR" or -NR'SO2R ", where R' and R" represent each independently of one another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, an alkyl or haloalkyl group, the alkyl group being optionally substituted with a cyano, amino, monoalkylamino group, dialkylamino or acylamino, · an aryl, arylalkyl, -X-aryl group, wherein X represents a group -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO -, -SO2-, -CO- or -CONH-, each substituted on the aryl portion with one or two substituents, whether identical or different, selected from: V a hydrogen atom or a halogen atom, a group or alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide, or a group -SOnR ', -COR', -C02R ', -OCOR', -CONR'R ", -NR'COR" or -NR'SO2R ", wherein R 'and R" each independently represent one of the other a hydrogen atom, an alkyl, haloalkyl group , and n has the value of 1 or 2, · a heterocycle group, -X-heterocycle, where X represents -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, each optionally substituted on the heterocycle moiety with one or two substituents, either identical or different, selected from: a hydrogen atom or a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkyl or dialkylamino, acid, ester, amide, mono or dialkylamide, or a group -SOnR \ -COR ', -CO2R' , -OCOR ', -CONR'R ", -NR'COR" or -NR'SO2R ", in do n of R 'and R "each represents independently of one another a hydrogen atom, an alkyl, haloalkyl group, and n has the value of 1 or 2, or · a cycloalkyl, cycloalkenyl, -X-cycloalkyl, -X group -cycloalkenyl, wherein X represents a group -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH- , each optionally substituted in the cyclic portion with one or two substituents either identical or different, selected from: a hydrogen atom or a halogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, hydroxyl, cyano, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide, or oxo, or a group - SOnR \ -COR ', -C02R \ -OCOR', -CONR'R ", -NR'COR "or -NR'SO2R", wherein R 'and R "each represent independently of one another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, and B represents a phenyl group or pyridine: - substituted in the ortho position with a N-cycloalkyl group such as piperidine or with a cyclohexyl, each optionally substituted with one or two substituents, either identical or different, selected from a hydrogen atom, an alkyl, haloalkyl, alkoxy, haloalkoxy, -X-aryl group, wherein X represents -O-, -NH- , -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, and / or, - optionally substituted with a halogen atom or with a alkyl or haloalkyl group. 5. The compounds according to any of claims 1 to 4, further characterized in that: G1 represents a bond or a saturated or unsaturated, straight or branched hydrocarbon chain, comprising 1-4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, preferably a bond or a hydrocarbon chain comprising one or two carbon atoms, G2 represents a group , wherein n is an integer comprised between 1 and 4, and m is an integer having the value of 1 or 2, preferably n has the value of 1 or 2, represents an alkoxy group, such as methoxy, preferably in the ortho position relative to R3, R2 represents a hydrogen or halogen atom, such as chlorine or bromine, or an alkyl group, such as methyl, preferably in the meta position in relation to R3, R3 represents an acid group or ester, A represents an aryl group such as phenyl, preferably substituted: in the meta or para position with: a halogen atom or an alkyl, haloalkyl, cyano, alkoxy, haloalkoxy, acylaminoalkyl or a -XR group , wherein X represents a group -O-, -NH-, -N (Alk) -, -N (COCH3) -, -S-, -SO-, -SO2-, -CO- or -CONH-, and R represents an arylalkyl, cycloalkyl or aryl group, each optionally substituted with one or two substituents, either identical or different, such as a halogen atom, an alkoxy group, chyl, haloalkyl, cyano, acyl, amino, monoalkylamino or dialkylamino, acid, ester, amide, mono or dialkylamide, or a group -SOnR \ -OCOR ', -NR'-COR "or -NR'SO2R", wherein R 'and R' represents each independently of one another a hydrogen atom, an alkyl group, haloalkyl, and n has the value of 1 or 2, a cycloalkyl, aryl, arylalkyl or heterocycle group, preferably N-cycloalkyl , each optionally substituted with one or two substituents, either identical or different, such as a halogen atom, an alkoxy, alkyl, haloalkyl, cyano, acyl, amino, monoalkylamino or dialkylamino group, acid, ester, amide, mono or dialkylamide, or a group -SOnR ', -OCOR', -NR'COR "or -NR'SO2R" ', wherein R' and R "each represent independently of one another a hydrogen atom, an alkyl group , haloalkyl and n has the value of 1 or 2, - and / or in the ortho or meta position with an alkyl group, and B represents an aryl group, preferably A phenyl is substituted, substituted in the ortho position with a heterocycle group, preferably an N-cycloalkyl, such as a piperidine group, and / or substituted in the ortho position with an alkyl group, such as a methyl. 6. The compounds according to any of claims 1 to 5, further characterized in that: d represents a bond or a saturated or unsaturated, linear or branched hydrocarbon chain, comprising 1-4 carbon atoms, optionally substituted with one or two alkyl groups, preferably identical, preferably a hydrocarbon chain or bond comprising 1 or 2 carbon atoms, G2 represents a group H, wherein n is an integer comprised between 1 and 4, and m is an integer having the value of 1 or 2, preferably n has the value of 1 or 2, Ri represents an alkoxy group, such as methoxy, of preferred manner in the ortho position relative to R3, R2 represents a hydrogen or halogen atom, such as chlorine or bromine, or an alkyl group, such as methyl, preferably at the meta position relative to R3, R3 represents a acid group or ester, A represents an aryl group such as phenyl, preferably substituted: - in the meta or para position with: · a halogen atom or a cyano, alkoxy, haloalkoxy, acylaminoalkyl or -XR group, wherein X represents -O-, -S-, -SO-, -SO2- or -CO- and R represents an arylalkyl, cycloalkyl or aryl group, each optionally substituted with one or two substituents, either identical or different, such as a halogen atom, an alkoxy or acyl group, or a cycloalkyl, aryl or arylalkyl group, each substituted optionally with one or two substituents, either identical or different, such as an acyl or alkoxy group, and - and / or in the ortho or meta position with an alkyl group, and B represents an aryl group, preferably a phenyl , • substituted in the ortho position with a heterocycle group, preferably an N-cycloalkyl, such as a piperidine group, and / or • substituted in the ortho position with an alkyl group, such as methyl. 7. The compounds according to any of claims 1 to 6, selected from the following group: 1) 5-bromo-2-methoxy-4- [N- (4-methoxy-phenyl) -N- hydrochloride ( 2- (piperidin-1-yl-phenyl) -hydrazinocarbonyl-methyl] -benzoic acid, 2) 5-bromo-2-methoxy-4- [N- (2-piperidin-1-yl-phenyl) -N hydrochloride - (4-trifluoromethoxy-phenyl) -hydrazinocarbonylmethyl] -benzoic acid, 3) 5-bromo-2-methoxy-4- [N- (3-methoxy-benzyl) -N- (2-piperidin-1-yl) hydrochloride phenyl) -hydrazinocarbonylmethyl] -benzoic acid, 4) 4- [N- (4-benzyloxy-phenyl) -N- (2-piperidin-1-yl-phenyl) hydrazinocarbonylmethyl] -5-bromo-2-methoxy acid hydrochloride -benzoic acid, 5) 5-bromo-4- hydrochloride. { N- [4- (4-fluoro-phenoxy) -phenyl] -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl} -2-methoxy-benzoic, 6) 5-bromo-2-methoxy-4- hydrochloride. { N- [2- (4-methoxy-phenyl) -ethyl] -N-2-piperidin-1-yl-phenyl) -hydrazino-carbonylmethyl} -benzoic acid, 7) 5-bromo-2-methoxy-4- [N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine-carbonylmethyl hydrochloride ] -benzoic acid, 7a) 5-bromo-2-methoxy-4- [N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazino-carbonylmethyl] - methyl benzoate, 8) 5-bromo-2-methoxy-4- [N- (4-methoxy-benzyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -benzoic acid hydrochloride, ) 5-bromo-4- [N- (4-cyclohexyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -2-methoxy-benzoic acid hydrochloride, 10) hydrochloride of 5-bromo-4- [N- (4-cyclohexyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -2-methoxy-benzoic acid; -bromo-2-methoxy-4- [N- (2-methyl-6-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxy-phenyl) -hydrazino-carbonylmethyl] -benzoic acid, 11) hydrochloride of the acid 5-bromo-2-methoxy-4- [N- (4'-methoxy-biphenyl-4-yl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonyl-methyl] -benzoic acid, 12) hydrochloride of 5-bromo-4- [N- (4-cyclohexyloxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -2-methoxy-benzoic acid 13) 5-bromo- 2-methoxy-4- [N- (4-phenoxy) phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -benzoic acid, 14) 5-bromo-4-hydrochloride. { N- [4- (4-chloro-phenoxy) -phenyl] -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl} -2-methoxy-benzoic, 5) 4- hydrochloride. { N- [4- (4-Fluoro-phenoxy) -phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl} -2-methoxy-benzoic, 16) 5-bromo-4- hydrochloride. { N- [4- (4-Fluoro-phenoxy) -phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazino-carbonyl-methyl} -2-methoxy-benzoic, 16a) 5-bromo-4-. { N- [4- (4-Fluoro-phenoxy) -phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazino-carbonyl-methyl} -2-M methyl benzoate, 17) 4- [N- (4-benzyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-bromo-2-methoxy acid hydrochloride -benzoic acid, 18) 4- [N- (4-bromo-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-chloro-2-methoxy-benzoic acid hydrochloride, 19) 4- [N- (3'-Acetyl-biphenyl-4-yl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-c 2-methoxy-benzoic acid hydrochloride, 20) hydrochloride 4- [N- (4'-Acetyl-biphenyl-4-yl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-chloro-2-mexoti-benzoic acid, 21) hydrochloride of 5-bromo-2-methoxy-4- [N- (3-phenoxy) -phenyl] -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -benzoic acid, 22) 5- Hydrochloride bromo-2-methoxy-4- [N- (4-phenylsulfanyl) -phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -benzoic acid, 23) 4- [N- ( 4-benzenesulfonyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-brom-2-methoxy-benzoic acid, 24) 4- [N- (4-benzenesulfinyl-phenyl) hydrochloride] -N - (2-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-bromo-2-methoxy-benzoic acid, 25) 2-methoxy-4- hydrochloride. { (E) -2- [N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonyl] -vinyl} -benzoic acid, 26) 5-bromo-2-methoxy-4- hydrochloride. { (E) -2- [N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazino-carbonyl] -vinyl} -benzoic acid, 27) 4- [N- (4-benzyl-phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-bromo-2-m benzoic acid hydrochloride , 28) 5-bromo-2-methoxy-4- [N- (4'-methoxy-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl) - hydrochloride hydrazino-carbonyl-methyl] -benzoic acid, 29) 4- [N- (Acetylamino-methyl) -phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -5-bromo-2-methoxy-benzoic acid hydrochloride , 30) 4- [N- (4-benzoyl) -phenyl] -N- (2-piperidin-1-yl enyl) -hydrazinocarbonylmethyl] -5-bromo-2-methoxybenzoic acid hydrochloride, 31) acid hydrochloride -bromo-4- [N- (4-cyano-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazinocarbonylmethyl] -2-methoxy-benzoic acid, 32) hydrochloride of the acid 4- [N- (4'-Acetyl-biphenyl-4-yl) -N- (2-methyl-6-piperidn-1-yl-enyl) -hydrazinocarbonylmethyl] -5-bromo-2-methox -benzoic acid, 33) 5-bromo-2-methoxy-4- [N- (4'-methoxy-2-methyl-biphenyl-4-yl) -N- (2-methyl-6-piperidine-) hydrochloride 1-yl-phenyl) -hydrazinocarbonylmethyl] -benzoic acid. 8 - Intermediates for the synthesis of the compounds as claimed in claim 7, selected from the following group: a) N- (4-methoxy-phenyl) -N- (2-piperidin-1-phenyl) - hydrazine, b) N- (2-piperidin-1-yl-phenyl) -N- (4-trifluoromethoxyphenyl) -hydrazine, c) N- (3-methoxy-benzyl) -N- (2-piperidin-1-yl) phenyl) -hydrazine, d) N- (4-benzyloxy-phenyl) -N- (2-piperidin-phenyl) -hydrazine, e), N- [4- (4-fluoro-phenoxy) -phenyl ] -N- (2-piperidin-1-yl-phenyl) -hydrazine, f) N- [2- (4-methoxy-phenyl) -ethyl] -N- (2-piperidin-1-yl-phenyl) - hydrazine, g) N- (4-methoxy-phenyl) -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine, h) N- (4-methoxy-benzyl) -N- (2 -piperidin-1-yl-phenyl) -hydrazine, i) N- (4-cyclohexyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine, j) N- (2-methyl-6 -piperidin-1-yl-phenyl) -N- (4-trifluoromethoxy-phenyl) -hydrazine, k) N- (4'-methoxy-biphenyl-4-yl) -N- (2-piperidin-1-yl- phenyl) -hydrazine, I) N- (4-cyclohexyloxy-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine, m) N- (4-phenoxy-phenyl) -N- (2- piperidin-1-yl-phenyl) -hydrazine , n) N- [4- (4-chloro-phenoxy) -phenyl] -N- (2-piperidin-1-yl-phenyl) -hydrazine, o) N- [4- (4-fiuoro-phenoxy) - phenyl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine, p) N- (4-benzyl-phenyl] -N- (2-piperidin-1-yl-phenyl) -hydrazine , q) N- (4-bromo-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine, r) N- (3-phenoxy-phenyl) -N- (2-piperidin-1- il-phenyl) -hydrazine, s) N- (4-phenylsulfanyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine, t) N- (4-benzyl-phenyl) -N - (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine, u) N- (4'-methoxy-biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl) phenyl) -hydrazine, v) N- (4-benzoyl-phenyl) -N- (2-piperidin-1-yl-phenyl) -hydrazine, w) N- [4 '- (2-methyl- [1, 3] dithian-2-yl) -biphenyl-4-yl] -N- (2-methyl-6-piperidin-1-yl-phenyl) -hydrazine, x) N- (4'-methoxy-2-methyl- biphenyl-4-yl) -N- (2-methyl-6-piperidin-1-yl-phenyl) hydrazine. 9. - A method for preparing the compounds of formula (I) as those claimed in any of claims 1 to 7, wherein G2 represents the radical W G I R, in accordance with claim 1, wherein the The following steps are carried out: 1) Reaction of the hydrazine function of a compound of formula (II) wherein A, B and Gi are in accordance with claim 1, with the function acid of a compound of formula (III) where R-i, R2 and G are as defined at the beginning, and P represents a group protector of the acid function, in order to obtain the compound of formula (IV) 2) the deprotection of the -CO2P group of the compound of formula (IV) by hydrolysis, in order to obtain the compound of formula (I) wherein W represents an oxygen atom and R3 is as defined at the beginning, 3) if necessary, the reaction of the compound of formula (I) obtained in step 2) or in addition to the compound of formula (IV) obtained in step 1) with a Lawesson reagent, so that a compound of formula (I) can be obtained, wherein W represents a sulfur atom. 10. A method for preparing the compounds of formula (I) as claimed in any of claims 1 to 7, wherein G2 represents the radical , according to claim 1, wherein the following steps are carried out: 1) the reaction in an acid medium of the compound of formula (V): (V) wherein Ri, R2 and G are in accordance with claim 1, and P represents a protective group of the acid function, such as a linear or branched (C C4) alkyl, in a formula compound (XXIV) wherein A, B and Gi are in accordance with claim 1, in order to obtain the compound of formula (IV): 2) the deprotection of the group -CO2P of the compound of formula (IV) by hydrolysis, in order to obtain the compound of formula (I) wherein W represents an oxygen atom and R3 is as defined at the beginning. 1. A pharmaceutical composition comprising at least one compound of formula (I), as claimed in any of claims 1 to 7, in association with a pharmaceutically acceptable excipient. 12. A compound of formula (I) as claimed in any of claims 1 to 7, for use as a drug. 13. The use of a compound of formula (I) as claimed in any of claims 1 to 7, for preparing a medicament useful for treating or preventing an infection with the papillomavirus. 14. The use as claimed in claim 13, wherein the medicament is useful for treating or preventing injuries and diseases associated with the papillomavirus. 15. - The use as claimed in claim 13 or 14, wherein the medicament is useful for the treatment or prevention of anogenital warts, such as condylomata acuminata and condylomata, laryngeal papillomas, conjunctiva or buccal or other epithelial lesions such as recurrent respiratory papillomatosis and low-grade and high-grade intraepithelial neoplasms, bowenoid papulosis, warts (common wart, plantar wart, verruca mirmecia, superficial wart, flat wart, ...), verruciform epidermodysplasia, carcinomas, in particular anogenital carcinomas , and all the lesions associated with the papilloma virus.